Dépouillements

Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder / G. BUSSU in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 13 p. Titre : Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : G. BUSSU, Auteur ; E. J. H. JONES, Auteur ; Tony CHARMAN, Auteur ; M. H. JOHNSON, Auteur ; Jan K. BUITELAAR, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : Adaptive behaviour  Autism  Infant siblings  Subgroups  Trajectories  Central NREC (approval codes 06/MRE02/73, 08/H0718/76), and one or both parents  gave informed consent to participate in the study.Not applicable.JKB has been a  consultant to/member of, an advisory board of, and/or a speaker for Janssen Cilag  BV, Eli Lilly, Lundbeck, Shire, Roche, Novartis, Medice, and Servier. He is  neither an employee nor a stock shareholder of any of these companies. TC has  received research grant support from the Medical Research Council (UK), the  National Institute of Health Research, Horizon 2020 and the Innovative Medicines  Initiative (both European Commission), MQ, Autistica, FP7 (European Commission),  the Charles Hawkins Fund, and the Waterloo Foundation. He has served as a  consultant to F. Hoffmann-La Roche, Ltd. He has received royalties from Sage  Publications and Guilford Publications. The present work is unrelated to these  relationships. The other authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is characterised by persisting difficulties in everyday functioning. Adaptive behaviour is heterogeneous across individuals with ASD, and it is not clear to what extent early development of adaptive behaviour relates to ASD outcome in toddlerhood. This study aims to identify subgroups of infants based on early development of adaptive skills and investigate their association with later ASD outcome. Methods: Adaptive behaviour was assessed on infants at high (n = 166) and low (n = 74) familial risk for ASD between 8 and 36 months using the Vineland Adaptive Behavior Scales (VABS-II). The four domains of VABS-II were modelled in parallel using growth mixture modelling to identify distinct classes of infants based on adaptive behaviour. Then, we associated class membership with clinical outcome and ASD symptoms at 36 months and longitudinal measures of cognitive development. Results: We observed three classes characterised by decreasing trajectories below age-appropriate norms (8.3%), stable trajectories around age-appropriate norms (73.8%), and increasing trajectories reaching average scores by age 2 (17.9%). Infants with declining adaptive behaviour had a higher risk (odds ratio (OR) = 4.40; confidence interval (CI) 1.90; 12.98) for ASD and higher parent-reported symptoms in the social, communication, and repetitive behaviour domains at 36 months. Furthermore, there was a discrepancy between adaptive and cognitive functioning as the class with improving adaptive skills showed stable cognitive development around average scores. Conclusions: Findings confirm the heterogeneity of trajectories of adaptive functioning in infancy, with a higher risk for ASD in toddlerhood linked to a plateau in the development of adaptive functioning after the first year of life. En ligne : https://dx.doi.org/10.1186/s13229-019-0264-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder [Texte imprimé et/ou numérique] / G. BUSSU, Auteur ; E. J. H. JONES, Auteur ; Tony CHARMAN, Auteur ; M. H. JOHNSON, Auteur ; Jan K. BUITELAAR, Auteur . - 13 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 13 p. Mots-clés : Adaptive behaviour  Autism  Infant siblings  Subgroups  Trajectories  Central NREC (approval codes 06/MRE02/73, 08/H0718/76), and one or both parents  gave informed consent to participate in the study.Not applicable.JKB has been a  consultant to/member of, an advisory board of, and/or a speaker for Janssen Cilag  BV, Eli Lilly, Lundbeck, Shire, Roche, Novartis, Medice, and Servier. He is  neither an employee nor a stock shareholder of any of these companies. TC has  received research grant support from the Medical Research Council (UK), the  National Institute of Health Research, Horizon 2020 and the Innovative Medicines  Initiative (both European Commission), MQ, Autistica, FP7 (European Commission),  the Charles Hawkins Fund, and the Waterloo Foundation. He has served as a  consultant to F. Hoffmann-La Roche, Ltd. He has received royalties from Sage  Publications and Guilford Publications. The present work is unrelated to these  relationships. The other authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is characterised by persisting difficulties in everyday functioning. Adaptive behaviour is heterogeneous across individuals with ASD, and it is not clear to what extent early development of adaptive behaviour relates to ASD outcome in toddlerhood. This study aims to identify subgroups of infants based on early development of adaptive skills and investigate their association with later ASD outcome. Methods: Adaptive behaviour was assessed on infants at high (n = 166) and low (n = 74) familial risk for ASD between 8 and 36 months using the Vineland Adaptive Behavior Scales (VABS-II). The four domains of VABS-II were modelled in parallel using growth mixture modelling to identify distinct classes of infants based on adaptive behaviour. Then, we associated class membership with clinical outcome and ASD symptoms at 36 months and longitudinal measures of cognitive development. Results: We observed three classes characterised by decreasing trajectories below age-appropriate norms (8.3%), stable trajectories around age-appropriate norms (73.8%), and increasing trajectories reaching average scores by age 2 (17.9%). Infants with declining adaptive behaviour had a higher risk (odds ratio (OR) = 4.40; confidence interval (CI) 1.90; 12.98) for ASD and higher parent-reported symptoms in the social, communication, and repetitive behaviour domains at 36 months. Furthermore, there was a discrepancy between adaptive and cognitive functioning as the class with improving adaptive skills showed stable cognitive development around average scores. Conclusions: Findings confirm the heterogeneity of trajectories of adaptive functioning in infancy, with a higher risk for ASD in toddlerhood linked to a plateau in the development of adaptive functioning after the first year of life. En ligne : https://dx.doi.org/10.1186/s13229-019-0264-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism / F. UZEFOVSKY in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 12 p. Titre : The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism Type de document : Texte imprimé et/ou numérique Auteurs : F. UZEFOVSKY, Auteur ; Richard A. I. BETHLEHEM, Auteur ; S. SHAMAY-TSOORY, Auteur ; A. RUIGROK, Auteur ; R. HOLT, Auteur ; M. SPENCER, Auteur ; L. CHURA, Auteur ; V. WARRIER, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Edward T. BULLMORE, Auteur ; J. SUCKLING, Auteur ; D. FLORIS, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autism  Imaging genetics  Oxytocin receptor  Supramarginal gyrus  fMRI  the relevant national and institutional committees on human experimentation and  with the Declaration of Helsinki of 1975, as revised in 2008.Not applicable.The  authors declare that they have no competing interests.Springer Nature remains  neutral with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the oxytocin receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Methods: Participants were adolescents (mean age = 14.7 +/- 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the 'Reading the Mind in the Eyes' Test (Eyes Test). Results: Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. Conclusions: This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism. En ligne : https://dx.doi.org/10.1186/s13229-019-0258-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism [Texte imprimé et/ou numérique] / F. UZEFOVSKY, Auteur ; Richard A. I. BETHLEHEM, Auteur ; S. SHAMAY-TSOORY, Auteur ; A. RUIGROK, Auteur ; R. HOLT, Auteur ; M. SPENCER, Auteur ; L. CHURA, Auteur ; V. WARRIER, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Edward T. BULLMORE, Auteur ; J. SUCKLING, Auteur ; D. FLORIS, Auteur ; Simon BARON-COHEN, Auteur . - 12 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 12 p. Mots-clés : Autism  Imaging genetics  Oxytocin receptor  Supramarginal gyrus  fMRI  the relevant national and institutional committees on human experimentation and  with the Declaration of Helsinki of 1975, as revised in 2008.Not applicable.The  authors declare that they have no competing interests.Springer Nature remains  neutral with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the oxytocin receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Methods: Participants were adolescents (mean age = 14.7 +/- 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the 'Reading the Mind in the Eyes' Test (Eyes Test). Results: Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. Conclusions: This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism. En ligne : https://dx.doi.org/10.1186/s13229-019-0258-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

A multifaceted approach for analyzing complex phenotypic data in rodent models of autism / I. DAS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 11 p. Titre : A multifaceted approach for analyzing complex phenotypic data in rodent models of autism Type de document : Texte imprimé et/ou numérique Auteurs : I. DAS, Auteur ; M. A. ESTEVEZ, Auteur ; A. A. SARKAR, Auteur ; Sharmila BANERJEE-BASU, Auteur Article en page(s) : 11 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism (MIM 209850) is a multifactorial disorder with a broad clinical presentation. A number of high-confidence ASD risk genes are known; however, the contribution of non-genetic environmental factors towards ASD remains largely uncertain. Here, we present a bioinformatics resource of genetic and induced models of ASD developed using a shared annotation platform. Using this data, we depict the intricate trends in the research approaches to analyze rodent models of ASD. We identify the top 30 most frequently studied phenotypes extracted from rodent models of ASD based on 787 publications. As expected, many of these include animal model equivalents of the "core" phenotypes associated with ASD, such as impairments in social behavior and repetitive behavior, as well as several comorbid features of ASD including anxiety, seizures, and motor-control deficits. These phenotypes have also been studied in models based on a broad range of environmental inducers present in the database, of which gestational exposure to valproic acid (VPA) and maternal immune activation models comprising lipopolysaccharide (LPS) and poly I:C are the most studied. In our unique dataset of rescue models, we identify 24 pharmaceutical agents tested on established models derived from various ASD genes and CNV loci for their efficacy in mitigating symptoms relevant for ASD. As a case study, we analyze a large collection of Shank3 mouse models providing a high-resolution view of the in vivo role of this high-confidence ASD gene, which is the gateway towards understanding and dissecting the heterogeneous phenotypes seen in single-gene models of ASD. The trends described in this study could be useful for researchers to compare ASD models and to establish a complete profile for all relevant animal models in ASD research. En ligne : https://dx.doi.org/10.1186/s13229-019-0263-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] A multifaceted approach for analyzing complex phenotypic data in rodent models of autism [Texte imprimé et/ou numérique] / I. DAS, Auteur ; M. A. ESTEVEZ, Auteur ; A. A. SARKAR, Auteur ; Sharmila BANERJEE-BASU, Auteur . - 11 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 11 p. Index. décimale : PER Périodiques Résumé : Autism (MIM 209850) is a multifactorial disorder with a broad clinical presentation. A number of high-confidence ASD risk genes are known; however, the contribution of non-genetic environmental factors towards ASD remains largely uncertain. Here, we present a bioinformatics resource of genetic and induced models of ASD developed using a shared annotation platform. Using this data, we depict the intricate trends in the research approaches to analyze rodent models of ASD. We identify the top 30 most frequently studied phenotypes extracted from rodent models of ASD based on 787 publications. As expected, many of these include animal model equivalents of the "core" phenotypes associated with ASD, such as impairments in social behavior and repetitive behavior, as well as several comorbid features of ASD including anxiety, seizures, and motor-control deficits. These phenotypes have also been studied in models based on a broad range of environmental inducers present in the database, of which gestational exposure to valproic acid (VPA) and maternal immune activation models comprising lipopolysaccharide (LPS) and poly I:C are the most studied. In our unique dataset of rescue models, we identify 24 pharmaceutical agents tested on established models derived from various ASD genes and CNV loci for their efficacy in mitigating symptoms relevant for ASD. As a case study, we analyze a large collection of Shank3 mouse models providing a high-resolution view of the in vivo role of this high-confidence ASD gene, which is the gateway towards understanding and dissecting the heterogeneous phenotypes seen in single-gene models of ASD. The trends described in this study could be useful for researchers to compare ASD models and to establish a complete profile for all relevant animal models in ASD research. En ligne : https://dx.doi.org/10.1186/s13229-019-0263-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Atypical event-related potentials revealed during the passive parts of a Go-NoGo task in autism spectrum disorder: a case-control study / A. L. HOYLAND in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 10 p. Titre : Atypical event-related potentials revealed during the passive parts of a Go-NoGo task in autism spectrum disorder: a case-control study Type de document : Texte imprimé et/ou numérique Auteurs : A. L. HOYLAND, Auteur ; T. NAERLAND, Auteur ; M. ENGSTROM, Auteur ; T. TORSKE, Auteur ; S. LYDERSEN, Auteur ; Ole A. ANDREASSEN, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : *asd  *erp  *n1  *P3a  *Passive condition  Research Ethics South East (2013/1236/REK South-East). Written informed consent  was obtained from participants and/ or parents necessary due to age.The authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: The core features of autism spectrum disorder (ASD) are easily recognizable in non-structured clinical and real-life situations. The features are often difficult to capture in structured laboratory settings, and the results from tests do not necessarily reflect symptom severity. We investigated neurophysiological processing in the passive parts of a cued Go-NoGo task, using the active parts of the test as a comparator. Methods: Forty-nine adolescents diagnosed with ASD and 49 typically developing (TD) adolescents (age 12-21 years) were included. Daily life executive function was assessed with the Behavior Rating Inventory of Executive Function (BRIEF). We applied a visual cued Go-NoGo task and recorded event-related potentials (ERPs). We investigated occipital N1, a component related to early perception of visual stimuli, and P3a, a fronto-central component related to switching of attention, in the passive and active parts of the test. Results: During the passive parts, the ASD group had statistically significantly longer N1 latency (p < 0.001, Cohens d = 0.75) and enhanced amplitude of P3a (p = 0.002, Cohens d = 0.64) compared to the TD, while no significant differences were observed in the active parts. Both components correlated significantly with the Behavioral Regulation Index of the BRIEF (partial correlation r = 0.35, p = 0.003). Conclusion: Delayed N1 response, indicating altered visual perception, and enhanced P3a response, indicating increased neural activation related to attention allocation, were found during the passive parts of a Go-NoGo task in ASD participants. These abnormal ERP signals in the non-structured settings were associated with everyday executive function, suggesting that neurophysiolocal measures related to atypical control of alertness and "hyper-awareness" underlie daily life dysfunction in ASD. Assessments during passive settings have a potential to reveal core neurobiological substrates of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0259-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Atypical event-related potentials revealed during the passive parts of a Go-NoGo task in autism spectrum disorder: a case-control study [Texte imprimé et/ou numérique] / A. L. HOYLAND, Auteur ; T. NAERLAND, Auteur ; M. ENGSTROM, Auteur ; T. TORSKE, Auteur ; S. LYDERSEN, Auteur ; Ole A. ANDREASSEN, Auteur . - 10 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 10 p. Mots-clés : *asd  *erp  *n1  *P3a  *Passive condition  Research Ethics South East (2013/1236/REK South-East). Written informed consent  was obtained from participants and/ or parents necessary due to age.The authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: The core features of autism spectrum disorder (ASD) are easily recognizable in non-structured clinical and real-life situations. The features are often difficult to capture in structured laboratory settings, and the results from tests do not necessarily reflect symptom severity. We investigated neurophysiological processing in the passive parts of a cued Go-NoGo task, using the active parts of the test as a comparator. Methods: Forty-nine adolescents diagnosed with ASD and 49 typically developing (TD) adolescents (age 12-21 years) were included. Daily life executive function was assessed with the Behavior Rating Inventory of Executive Function (BRIEF). We applied a visual cued Go-NoGo task and recorded event-related potentials (ERPs). We investigated occipital N1, a component related to early perception of visual stimuli, and P3a, a fronto-central component related to switching of attention, in the passive and active parts of the test. Results: During the passive parts, the ASD group had statistically significantly longer N1 latency (p < 0.001, Cohens d = 0.75) and enhanced amplitude of P3a (p = 0.002, Cohens d = 0.64) compared to the TD, while no significant differences were observed in the active parts. Both components correlated significantly with the Behavioral Regulation Index of the BRIEF (partial correlation r = 0.35, p = 0.003). Conclusion: Delayed N1 response, indicating altered visual perception, and enhanced P3a response, indicating increased neural activation related to attention allocation, were found during the passive parts of a Go-NoGo task in ASD participants. These abnormal ERP signals in the non-structured settings were associated with everyday executive function, suggesting that neurophysiolocal measures related to atypical control of alertness and "hyper-awareness" underlie daily life dysfunction in ASD. Assessments during passive settings have a potential to reveal core neurobiological substrates of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0259-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Selection bias on intellectual ability in autism research: a cross-sectional review and meta-analysis / G. RUSSELL in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 9 p. Titre : Selection bias on intellectual ability in autism research: a cross-sectional review and meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : G. RUSSELL, Auteur ; W. MANDY, Auteur ; D. ELLIOTT, Auteur ; R. WHITE, Auteur ; T. PITTWOOD, Auteur ; T. FORD, Auteur Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : *Autism  *Autism spectrum disorder  *Intellectual disability  *Nosology  *Selection bias  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Current global estimates suggest the proportion of the population with autism spectrum disorder (ASD) who have intellectual disability (ID) is approximately 50%. Our objective was to ascertain the existence of selection bias due to under-inclusion of populations with ID across all fields of autism research. A sub-goal was to evaluate inconsistencies in reporting of findings. Methods: This review covers all original research published in 2016 in autism-specific journals with an impact factor greater than 3. Across 301 included studies, 100,245 participants had ASD. A random effects meta-analysis was used to estimate the proportion of participants without ID. Selection bias was defined as where more than 75% of participants did not have ID. Results: Meta-analysis estimated 94% of all participants identified as being on the autism spectrum in the studies reviewed did not have ID (95% CI 0.91-0.97). Eight out of ten studies demonstrated selection bias against participants with ID. The reporting of participant characteristics was generally poor: information about participants' intellectual ability was absent in 38% of studies (n = 114). Where there was selection bias on ID, only 31% of studies mentioned lack of generalisability as a limitation. Conclusions: We found selection bias against ID throughout all fields of autism research. We recommend transparent reporting about ID and strategies for inclusion for this much marginalised group. En ligne : https://dx.doi.org/10.1186/s13229-019-0260-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Selection bias on intellectual ability in autism research: a cross-sectional review and meta-analysis [Texte imprimé et/ou numérique] / G. RUSSELL, Auteur ; W. MANDY, Auteur ; D. ELLIOTT, Auteur ; R. WHITE, Auteur ; T. PITTWOOD, Auteur ; T. FORD, Auteur . - 9 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 9 p. Mots-clés : *Autism  *Autism spectrum disorder  *Intellectual disability  *Nosology  *Selection bias  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Current global estimates suggest the proportion of the population with autism spectrum disorder (ASD) who have intellectual disability (ID) is approximately 50%. Our objective was to ascertain the existence of selection bias due to under-inclusion of populations with ID across all fields of autism research. A sub-goal was to evaluate inconsistencies in reporting of findings. Methods: This review covers all original research published in 2016 in autism-specific journals with an impact factor greater than 3. Across 301 included studies, 100,245 participants had ASD. A random effects meta-analysis was used to estimate the proportion of participants without ID. Selection bias was defined as where more than 75% of participants did not have ID. Results: Meta-analysis estimated 94% of all participants identified as being on the autism spectrum in the studies reviewed did not have ID (95% CI 0.91-0.97). Eight out of ten studies demonstrated selection bias against participants with ID. The reporting of participant characteristics was generally poor: information about participants' intellectual ability was absent in 38% of studies (n = 114). Where there was selection bias on ID, only 31% of studies mentioned lack of generalisability as a limitation. Conclusions: We found selection bias against ID throughout all fields of autism research. We recommend transparent reporting about ID and strategies for inclusion for this much marginalised group. En ligne : https://dx.doi.org/10.1186/s13229-019-0260-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Autism prevalence in China is comparable to Western prevalence / X. SUN in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 7 p. Titre : Autism prevalence in China is comparable to Western prevalence Type de document : Texte imprimé et/ou numérique Auteurs : X. SUN, Auteur ; Carrie ALLISON, Auteur ; L. WEI, Auteur ; F. E. MATTHEWS, Auteur ; Bonnie AUYEUNG, Auteur ; Y. Y. WU, Auteur ; S. GRIFFITHS, Auteur ; J. ZHANG, Auteur ; Simon BARON-COHEN, Auteur ; Carol BRAYNE, Auteur Article en page(s) : 7 p. Langues : Anglais (eng) Mots-clés : *Autism  *Children  *China  *Diagnosis  *Prevalence  *Screening  University of Hong Kong and the Peking University Institutional Review Board.  Consent was provided to participants via the screening package before  participating. Participants were asked to indicate whether they continued to  consent at the end of the study.Not applicable.The authors declare that they have  no competing interests.Springer Nature remains neutral with regard to  jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism prevalence in the West is approximately 1% of school age children. Autism prevalence in China has been reported to be lower than in the West. This is likely due to at least two reasons: (1) most studies in China only included the special school population, overlooking the mainstream school population; and (2) most studies in China have not used contemporary screening and diagnostic methods. To address this, we tested total autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities. Methods: The study included a three-step process: (1) screening; (2) clinical assessment of 'screen positives' plus controls; and (3) research diagnostic assessment of those meeting clinical threshold for concerns at step 2. Prevalence estimates per 10,000 children aged 6-10 years old were weighted for study design using diagnostic criteria applied at the research assessment stage. Results: In Jilin City, 77 cases of autism were identified from a total population of 7258, equating to a prevalence of 108 per 10,000 (95% confidence interval (CI) 89, 130). In Shenzhen City: 21,420 children were screened and 35 cases of autism were identified, resulting in a mainstream prevalence of 42 per 10,000 (95% CI 20-89). In Jiamusi City, 16,358 children were screened, with 10 autism cases being identified, with a mainstream prevalence of 19 per 10,000 (95% CI 10-38). Conclusions: Results from Jilin City, where both mainstream and special school data were available, revealed a similar prevalence of autism in China to the West, at around 1%. Results from Shenzhen and Jiamusi cities, where only mainstream data were available, prevalence is also in line with Western estimates. In all three cities, new cases of autism were identified by the study in mainstream schools, reflecting current under-diagnosis. Non-significant variation across different cities is seen indicating the need to explore potential variation of autism across diverse Chinese regions with large sample sizes to achieve a fully robust national picture. En ligne : https://dx.doi.org/10.1186/s13229-018-0246-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Autism prevalence in China is comparable to Western prevalence [Texte imprimé et/ou numérique] / X. SUN, Auteur ; Carrie ALLISON, Auteur ; L. WEI, Auteur ; F. E. MATTHEWS, Auteur ; Bonnie AUYEUNG, Auteur ; Y. Y. WU, Auteur ; S. GRIFFITHS, Auteur ; J. ZHANG, Auteur ; Simon BARON-COHEN, Auteur ; Carol BRAYNE, Auteur . - 7 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 7 p. Mots-clés : *Autism  *Children  *China  *Diagnosis  *Prevalence  *Screening  University of Hong Kong and the Peking University Institutional Review Board.  Consent was provided to participants via the screening package before  participating. Participants were asked to indicate whether they continued to  consent at the end of the study.Not applicable.The authors declare that they have  no competing interests.Springer Nature remains neutral with regard to  jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism prevalence in the West is approximately 1% of school age children. Autism prevalence in China has been reported to be lower than in the West. This is likely due to at least two reasons: (1) most studies in China only included the special school population, overlooking the mainstream school population; and (2) most studies in China have not used contemporary screening and diagnostic methods. To address this, we tested total autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities. Methods: The study included a three-step process: (1) screening; (2) clinical assessment of 'screen positives' plus controls; and (3) research diagnostic assessment of those meeting clinical threshold for concerns at step 2. Prevalence estimates per 10,000 children aged 6-10 years old were weighted for study design using diagnostic criteria applied at the research assessment stage. Results: In Jilin City, 77 cases of autism were identified from a total population of 7258, equating to a prevalence of 108 per 10,000 (95% confidence interval (CI) 89, 130). In Shenzhen City: 21,420 children were screened and 35 cases of autism were identified, resulting in a mainstream prevalence of 42 per 10,000 (95% CI 20-89). In Jiamusi City, 16,358 children were screened, with 10 autism cases being identified, with a mainstream prevalence of 19 per 10,000 (95% CI 10-38). Conclusions: Results from Jilin City, where both mainstream and special school data were available, revealed a similar prevalence of autism in China to the West, at around 1%. Results from Shenzhen and Jiamusi cities, where only mainstream data were available, prevalence is also in line with Western estimates. In all three cities, new cases of autism were identified by the study in mainstream schools, reflecting current under-diagnosis. Non-significant variation across different cities is seen indicating the need to explore potential variation of autism across diverse Chinese regions with large sample sizes to achieve a fully robust national picture. En ligne : https://dx.doi.org/10.1186/s13229-018-0246-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice / E. PERVOLARAKI in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 8 p. Titre : The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice Type de document : Texte imprimé et/ou numérique Auteurs : E. PERVOLARAKI, Auteur ; A. L. TYSON, Auteur ; F. PIBIRI, Auteur ; S. L. POULTER, Auteur ; A. C. REICHELT, Auteur ; R. J. RODGERS, Auteur ; S. J. CLAPCOTE, Auteur ; C. LEVER, Auteur ; L. C. ANDREAE, Auteur ; J. DACHTLER, Auteur Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : *Autism  *Axons  *clarity  *Diffusion  *Imaging  *mri  *Social  *Structure  in accordance with the Animals (Scientific Procedures) Act 1986, and with the  approval of the University of Leeds and Durham University Animal Ethical and  Welfare Review Boards.Not applicableThe authors declare that they have no  competing interests.Springer Nature remains neutral with regard to jurisdictional  claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2alpha knockout (KO) model. Methods: Fixed brains of Nrxn2alpha KO mice underwent DTI using 9.4 T MRI, and diffusion properties of socially relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. Results: DTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2alpha KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. Conclusions: Our findings demonstrate that deleting a single neurexin gene (Nrxn2alpha) induces atypical structural connectivity within socially relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain. En ligne : https://dx.doi.org/10.1186/s13229-019-0261-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice [Texte imprimé et/ou numérique] / E. PERVOLARAKI, Auteur ; A. L. TYSON, Auteur ; F. PIBIRI, Auteur ; S. L. POULTER, Auteur ; A. C. REICHELT, Auteur ; R. J. RODGERS, Auteur ; S. J. CLAPCOTE, Auteur ; C. LEVER, Auteur ; L. C. ANDREAE, Auteur ; J. DACHTLER, Auteur . - 8 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 8 p. Mots-clés : *Autism  *Axons  *clarity  *Diffusion  *Imaging  *mri  *Social  *Structure  in accordance with the Animals (Scientific Procedures) Act 1986, and with the  approval of the University of Leeds and Durham University Animal Ethical and  Welfare Review Boards.Not applicableThe authors declare that they have no  competing interests.Springer Nature remains neutral with regard to jurisdictional  claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2alpha knockout (KO) model. Methods: Fixed brains of Nrxn2alpha KO mice underwent DTI using 9.4 T MRI, and diffusion properties of socially relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. Results: DTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2alpha KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. Conclusions: Our findings demonstrate that deleting a single neurexin gene (Nrxn2alpha) induces atypical structural connectivity within socially relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain. En ligne : https://dx.doi.org/10.1186/s13229-019-0261-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Rigor in science and science reporting: updated guidelines for submissions to Molecular Autism / Joseph D. BUXBAUM in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 6 p. Titre : Rigor in science and science reporting: updated guidelines for submissions to Molecular Autism Type de document : Texte imprimé et/ou numérique Auteurs : Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Chris ASHWIN, Auteur ; Catalina BETANCUR, Auteur ; Bhismadev CHAKRABARTI, Auteur ; J. N. CRAWLEY, Auteur ; R. A. HOEKSTRA, Auteur ; P. R. HOF, Auteur ; Meng-Chuan LAI, Auteur ; M. V. LOMBARDO, Auteur ; C. M. SCHUMANN, Auteur Article en page(s) : 6 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s13229-018-0249-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Rigor in science and science reporting: updated guidelines for submissions to Molecular Autism [Texte imprimé et/ou numérique] / Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Chris ASHWIN, Auteur ; Catalina BETANCUR, Auteur ; Bhismadev CHAKRABARTI, Auteur ; J. N. CRAWLEY, Auteur ; R. A. HOEKSTRA, Auteur ; P. R. HOF, Auteur ; Meng-Chuan LAI, Auteur ; M. V. LOMBARDO, Auteur ; C. M. SCHUMANN, Auteur . - 6 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 6 p. Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s13229-018-0249-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Haploinsufficiency of autism causative gene Tbr1 impairs olfactory discrimination and neuronal activation of the olfactory system in mice / T. N. HUANG in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 5 p. Titre : Haploinsufficiency of autism causative gene Tbr1 impairs olfactory discrimination and neuronal activation of the olfactory system in mice Type de document : Texte imprimé et/ou numérique Auteurs : T. N. HUANG, Auteur ; T. L. YEN, Auteur ; L. R. QIU, Auteur ; H. C. CHUANG, Auteur ; J. P. LERCH, Auteur ; Y. P. HSUEH, Auteur Article en page(s) : 5 p. Langues : Anglais (eng) Mots-clés : *Autism spectrum disorders  *c-fos  *D-cycloserine  *Neuronal activation  *Olfactory bulb  *Olfactory discrimination  *T-brain-1  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) exhibit two clusters of core symptoms, i.e., social and communication impairment, and repetitive behaviors and sensory abnormalities. Our previous study demonstrated that TBR1, a causative gene of ASD, controls axonal projection and neuronal activation of amygdala and regulates social interaction and vocal communication in a mouse model. Behavioral defects caused by Tbr1 haploinsufficiency can be ameliorated by increasing neural activity via D-cycloserine treatment, an N-methyl-D-aspartate receptor (NMDAR) coagonist. In this report, we investigate the role of TBR1 in regulating olfaction and test whether D-cycloserine can also improve olfactory defects in Tbr1 mutant mice. Methods: We used Tbr1 (+/-) mice as a model to investigate the function of TBR1 in olfactory sensation and discrimination of non-social odors. We employed a behavioral assay to characterize the olfactory defects of Tbr1 (+/-) mice. Magnetic resonance imaging (MRI) and histological analysis were applied to characterize anatomical features. Immunostaining was performed to further analyze differences in expression of TBR1 subfamily members (namely TBR1, TBR2, and TBX21), interneuron populations, and dendritic abnormalities in olfactory bulbs. Finally, C-FOS staining was used to monitor neuronal activation of the olfactory system upon odor stimulation. Results: Tbr1 (+/-) mice exhibited smaller olfactory bulbs and anterior commissures, reduced interneuron populations, and an abnormal dendritic morphology of mitral cells in the olfactory bulbs. Tbr1 haploinsufficiency specifically impaired olfactory discrimination but not olfactory sensation. Neuronal activation upon odorant stimulation was reduced in the glomerular layer of Tbr1 (+/-) olfactory bulbs. Furthermore, although the sizes of piriform and perirhinal cortices were not affected by Tbr1 deficiency, neuronal activation was reduced in these two cortical regions in response to odorant stimulation. These results suggest an impairment of neuronal activation in olfactory bulbs and defective connectivity from olfactory bulbs to the upper olfactory system in Tbr1 (+/-) mice. Systemic administration of D-cycloserine, an NMDAR co-agonist, ameliorated olfactory discrimination in Tbr1 (+/-) mice, suggesting that increased neuronal activity has a beneficial effect on Tbr1 deficiency. Conclusions: Tbr1 regulates neural circuits and activity in the olfactory system to control olfaction. Tbr1 (+/-) mice can serve as a suitable model for revealing how an autism causative gene controls neuronal circuits, neural activity, and autism-related behaviors. En ligne : https://dx.doi.org/10.1186/s13229-019-0257-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Haploinsufficiency of autism causative gene Tbr1 impairs olfactory discrimination and neuronal activation of the olfactory system in mice [Texte imprimé et/ou numérique] / T. N. HUANG, Auteur ; T. L. YEN, Auteur ; L. R. QIU, Auteur ; H. C. CHUANG, Auteur ; J. P. LERCH, Auteur ; Y. P. HSUEH, Auteur . - 5 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 5 p. Mots-clés : *Autism spectrum disorders  *c-fos  *D-cycloserine  *Neuronal activation  *Olfactory bulb  *Olfactory discrimination  *T-brain-1  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) exhibit two clusters of core symptoms, i.e., social and communication impairment, and repetitive behaviors and sensory abnormalities. Our previous study demonstrated that TBR1, a causative gene of ASD, controls axonal projection and neuronal activation of amygdala and regulates social interaction and vocal communication in a mouse model. Behavioral defects caused by Tbr1 haploinsufficiency can be ameliorated by increasing neural activity via D-cycloserine treatment, an N-methyl-D-aspartate receptor (NMDAR) coagonist. In this report, we investigate the role of TBR1 in regulating olfaction and test whether D-cycloserine can also improve olfactory defects in Tbr1 mutant mice. Methods: We used Tbr1 (+/-) mice as a model to investigate the function of TBR1 in olfactory sensation and discrimination of non-social odors. We employed a behavioral assay to characterize the olfactory defects of Tbr1 (+/-) mice. Magnetic resonance imaging (MRI) and histological analysis were applied to characterize anatomical features. Immunostaining was performed to further analyze differences in expression of TBR1 subfamily members (namely TBR1, TBR2, and TBX21), interneuron populations, and dendritic abnormalities in olfactory bulbs. Finally, C-FOS staining was used to monitor neuronal activation of the olfactory system upon odor stimulation. Results: Tbr1 (+/-) mice exhibited smaller olfactory bulbs and anterior commissures, reduced interneuron populations, and an abnormal dendritic morphology of mitral cells in the olfactory bulbs. Tbr1 haploinsufficiency specifically impaired olfactory discrimination but not olfactory sensation. Neuronal activation upon odorant stimulation was reduced in the glomerular layer of Tbr1 (+/-) olfactory bulbs. Furthermore, although the sizes of piriform and perirhinal cortices were not affected by Tbr1 deficiency, neuronal activation was reduced in these two cortical regions in response to odorant stimulation. These results suggest an impairment of neuronal activation in olfactory bulbs and defective connectivity from olfactory bulbs to the upper olfactory system in Tbr1 (+/-) mice. Systemic administration of D-cycloserine, an NMDAR co-agonist, ameliorated olfactory discrimination in Tbr1 (+/-) mice, suggesting that increased neuronal activity has a beneficial effect on Tbr1 deficiency. Conclusions: Tbr1 regulates neural circuits and activity in the olfactory system to control olfaction. Tbr1 (+/-) mice can serve as a suitable model for revealing how an autism causative gene controls neuronal circuits, neural activity, and autism-related behaviors. En ligne : https://dx.doi.org/10.1186/s13229-019-0257-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Sensory over-responsivity: parent report, direct assessment measures, and neural architecture / Teresa TAVASSOLI in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 4 p. Titre : Sensory over-responsivity: parent report, direct assessment measures, and neural architecture Type de document : Texte imprimé et/ou numérique Auteurs : Teresa TAVASSOLI, Auteur ; Annie BRANDES-AITKEN, Auteur ; R. CHU, Auteur ; L. PORTER, Auteur ; S. SCHOEN, Auteur ; L. J. MILLER, Auteur ; M. R. GERDES, Auteur ; J. OWEN, Auteur ; P. MUKHERJEE, Auteur ; E. J. MARCO, Auteur Article en page(s) : 4 p. Langues : Anglais (eng) Mots-clés : *Assessment  *Diffusion Tensor Imaging  *Neurodevelopmental disorder  *Sensory over-responsivity  *Sensory processing disorder  *autism  of California, San Francisco (10-01940). Written consent was collected from  parents of the participants.All recruited participants/parents have given consent  for publication during the recruitment process.The authors declare that they have  no competing interests.Springer Nature remains neutral with regard to  jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Sensory processing difficulties are common across neurodevelopmental disorders. Thus, reliable measures are needed to understand the biological underpinnings of these differences. This study aimed to define a scoring methodology specific to auditory (AOR) and tactile (TOR) over-responsivity. Second, in a pilot cohort using MRI Diffusion Tensor Imaging, we performed a proof of concept study of whether children with AOR showed measurable differences in their white matter integrity. Methods: This study included children with AOR and TOR from a mixed neurodevelopmental disorder cohort including autism and sensory processing dysfunction (n = 176) as well as neurotypical children (n = 128). We established cohorts based on sensory over-responsivity using parent report (Short Sensory Profile (SSP)) and direct assessment (Sensory Processing-Three Dimensions: Assessment (SP-3D:A)) measures. With a subset of the children (n = 39), group comparisons, based on AOR phenotype, were conducted comparing the white matter fractional anisotropy in 23 regions of interest. Results: Using direct assessment, 31% of the children with neurodevelopmental disorders had AOR and 27% had TOR. The inter-test agreement between SSP and SP-3D:A for AOR was 65% and TOR was 50%. Children with AOR had three white matter tracts showing decreased fractional anisotropy relative to children without AOR. Conclusions: This study identified cut-off scores for AOR and TOR using the SSP parent report and SP-3D:A observation. A combination of questionnaire and direct observation measures should be used in clinical and research settings. The SSP parent report and SP-3D:A direct observation ratings overlapped moderately for sensory related behaviors. Based on these preliminary structural neuroimaging results, we suggest a putative neural network may contribute to AOR. En ligne : https://dx.doi.org/10.1186/s13229-019-0255-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Sensory over-responsivity: parent report, direct assessment measures, and neural architecture [Texte imprimé et/ou numérique] / Teresa TAVASSOLI, Auteur ; Annie BRANDES-AITKEN, Auteur ; R. CHU, Auteur ; L. PORTER, Auteur ; S. SCHOEN, Auteur ; L. J. MILLER, Auteur ; M. R. GERDES, Auteur ; J. OWEN, Auteur ; P. MUKHERJEE, Auteur ; E. J. MARCO, Auteur . - 4 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 4 p. Mots-clés : *Assessment  *Diffusion Tensor Imaging  *Neurodevelopmental disorder  *Sensory over-responsivity  *Sensory processing disorder  *autism  of California, San Francisco (10-01940). Written consent was collected from  parents of the participants.All recruited participants/parents have given consent  for publication during the recruitment process.The authors declare that they have  no competing interests.Springer Nature remains neutral with regard to  jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Sensory processing difficulties are common across neurodevelopmental disorders. Thus, reliable measures are needed to understand the biological underpinnings of these differences. This study aimed to define a scoring methodology specific to auditory (AOR) and tactile (TOR) over-responsivity. Second, in a pilot cohort using MRI Diffusion Tensor Imaging, we performed a proof of concept study of whether children with AOR showed measurable differences in their white matter integrity. Methods: This study included children with AOR and TOR from a mixed neurodevelopmental disorder cohort including autism and sensory processing dysfunction (n = 176) as well as neurotypical children (n = 128). We established cohorts based on sensory over-responsivity using parent report (Short Sensory Profile (SSP)) and direct assessment (Sensory Processing-Three Dimensions: Assessment (SP-3D:A)) measures. With a subset of the children (n = 39), group comparisons, based on AOR phenotype, were conducted comparing the white matter fractional anisotropy in 23 regions of interest. Results: Using direct assessment, 31% of the children with neurodevelopmental disorders had AOR and 27% had TOR. The inter-test agreement between SSP and SP-3D:A for AOR was 65% and TOR was 50%. Children with AOR had three white matter tracts showing decreased fractional anisotropy relative to children without AOR. Conclusions: This study identified cut-off scores for AOR and TOR using the SSP parent report and SP-3D:A observation. A combination of questionnaire and direct observation measures should be used in clinical and research settings. The SSP parent report and SP-3D:A direct observation ratings overlapped moderately for sensory related behaviors. Based on these preliminary structural neuroimaging results, we suggest a putative neural network may contribute to AOR. En ligne : https://dx.doi.org/10.1186/s13229-019-0255-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism / D. M. JAMES in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 3 p. Titre : Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism Type de document : Texte imprimé et/ou numérique Auteurs : D. M. JAMES, Auteur ; R. A. KOZOL, Auteur ; Y. KAJIWARA, Auteur ; A. L. WAHL, Auteur ; E. C. STORRS, Auteur ; Joseph D. BUXBAUM, Auteur ; M. KLEIN, Auteur ; B. MOSHIREE, Auteur ; J. E. DALLMAN, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : *Digestive transit  *Enteroendocrine  *Peristaltic rate  *Phelan-McDermid syndrome  approved by the Institutional Animal Care and Use Committee of University of  Miami.The authors declare that they have no competing interests.Springer Nature  remains neutral with regard to jurisdictional claims in published maps and  institutional affiliations. Index. décimale : PER Périodiques Résumé : Background and aims: Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the SHANK3 gene. Methods: To generate a zebrafish model of PMS, we used CRISPR/Cas9 to introduce clinically related C-terminal frameshift mutations in shank3a and shank3b zebrafish paralogues (shank3abDeltaC). Because PMS is caused by SHANK3 haploinsufficiency, we assessed the digestive tract (DT) structure and function in zebrafish shank3abDeltaC (+/-) heterozygotes. Human SHANK3 mRNA was then used to rescue DT phenotypes in larval zebrafish. Results: Significantly slower rates of DT peristaltic contractions (p < 0.001) with correspondingly prolonged passage time (p < 0.004) occurred in shank3abDeltaC (+/-) mutants. Rescue injections of mRNA encoding the longest human SHANK3 isoform into shank3abDeltaC (+/-) mutants produced larvae with intestinal bulb emptying similar to wild type (WT), but still deficits in posterior intestinal motility. Serotonin-positive enteroendocrine cells (EECs) were significantly reduced in both shank3abDeltaC (+/-) and shank3abDeltaC (-/-) mutants (p < 0.05) while enteric neuron counts and overall structure of the DT epithelium, including goblet cell number, were unaffected in shank3abDeltaC (+/-) larvae. Conclusions: Our data and rescue experiments support mutations in SHANK3 as causal for GI transit and motility abnormalities. Reductions in serotonin-positive EECs and serotonin-filled ENS boutons suggest an endocrine/neural component to this dysmotility. This is the first study to date demonstrating DT dysmotility in a zebrafish single gene mutant model of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0250-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism [Texte imprimé et/ou numérique] / D. M. JAMES, Auteur ; R. A. KOZOL, Auteur ; Y. KAJIWARA, Auteur ; A. L. WAHL, Auteur ; E. C. STORRS, Auteur ; Joseph D. BUXBAUM, Auteur ; M. KLEIN, Auteur ; B. MOSHIREE, Auteur ; J. E. DALLMAN, Auteur . - 3 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 3 p. Mots-clés : *Digestive transit  *Enteroendocrine  *Peristaltic rate  *Phelan-McDermid syndrome  approved by the Institutional Animal Care and Use Committee of University of  Miami.The authors declare that they have no competing interests.Springer Nature  remains neutral with regard to jurisdictional claims in published maps and  institutional affiliations. Index. décimale : PER Périodiques Résumé : Background and aims: Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the SHANK3 gene. Methods: To generate a zebrafish model of PMS, we used CRISPR/Cas9 to introduce clinically related C-terminal frameshift mutations in shank3a and shank3b zebrafish paralogues (shank3abDeltaC). Because PMS is caused by SHANK3 haploinsufficiency, we assessed the digestive tract (DT) structure and function in zebrafish shank3abDeltaC (+/-) heterozygotes. Human SHANK3 mRNA was then used to rescue DT phenotypes in larval zebrafish. Results: Significantly slower rates of DT peristaltic contractions (p < 0.001) with correspondingly prolonged passage time (p < 0.004) occurred in shank3abDeltaC (+/-) mutants. Rescue injections of mRNA encoding the longest human SHANK3 isoform into shank3abDeltaC (+/-) mutants produced larvae with intestinal bulb emptying similar to wild type (WT), but still deficits in posterior intestinal motility. Serotonin-positive enteroendocrine cells (EECs) were significantly reduced in both shank3abDeltaC (+/-) and shank3abDeltaC (-/-) mutants (p < 0.05) while enteric neuron counts and overall structure of the DT epithelium, including goblet cell number, were unaffected in shank3abDeltaC (+/-) larvae. Conclusions: Our data and rescue experiments support mutations in SHANK3 as causal for GI transit and motility abnormalities. Reductions in serotonin-positive EECs and serotonin-filled ENS boutons suggest an endocrine/neural component to this dysmotility. This is the first study to date demonstrating DT dysmotility in a zebrafish single gene mutant model of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0250-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Lower circulating endocannabinoid levels in children with autism spectrum disorder / Adi ARAN in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 2 p. Titre : Lower circulating endocannabinoid levels in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Adi ARAN, Auteur ; M. EYLON, Auteur ; M. HAREL, Auteur ; L. POLIANSKI, Auteur ; A. NEMIROVSKI, Auteur ; S. TEPPER, Auteur ; A. SCHNAPP, Auteur ; Hanoch CASSUTO, Auteur ; N. WATTAD, Auteur ; J. TAM, Auteur Article en page(s) : 2 p. Langues : Anglais (eng) Mots-clés : *2-arachidonoylglycerol  *Anandamide  *Arachidonic acid  *Autism spectrum disorder  *Biomarkers  *Cannabinoids  *Endocannabinoid system  *N-arachidonoylethanolamine  *N-oleoylethanolamine  *N-palmitoylethanolamine  Board and Israeli Ministry of Health prior to participant enrollment.  Participants' parents provided written consent prior to initiation of any  experimental procedures, and written assent was obtained from participants when  appropriate.Not applicable.The authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods: Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 +/- 4.1, range 6-21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 +/- 4.3, range 5.5-21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results: Children with ASD had lower levels (pmol/mL, mean +/- SEM) of AEA (0.722 +/- 0.045 vs. 1.252 +/- 0.072, P < 0.0001, effect size 0.91), OEA (17.3 +/- 0.80 vs. 27.8 +/- 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 +/- 0.32 vs. 7.15 +/- 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions: We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid "tone" in the brain, as found in animal models of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0256-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Lower circulating endocannabinoid levels in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Adi ARAN, Auteur ; M. EYLON, Auteur ; M. HAREL, Auteur ; L. POLIANSKI, Auteur ; A. NEMIROVSKI, Auteur ; S. TEPPER, Auteur ; A. SCHNAPP, Auteur ; Hanoch CASSUTO, Auteur ; N. WATTAD, Auteur ; J. TAM, Auteur . - 2 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 2 p. Mots-clés : *2-arachidonoylglycerol  *Anandamide  *Arachidonic acid  *Autism spectrum disorder  *Biomarkers  *Cannabinoids  *Endocannabinoid system  *N-arachidonoylethanolamine  *N-oleoylethanolamine  *N-palmitoylethanolamine  Board and Israeli Ministry of Health prior to participant enrollment.  Participants' parents provided written consent prior to initiation of any  experimental procedures, and written assent was obtained from participants when  appropriate.Not applicable.The authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods: Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 +/- 4.1, range 6-21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 +/- 4.3, range 5.5-21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results: Children with ASD had lower levels (pmol/mL, mean +/- SEM) of AEA (0.722 +/- 0.045 vs. 1.252 +/- 0.072, P < 0.0001, effect size 0.91), OEA (17.3 +/- 0.80 vs. 27.8 +/- 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 +/- 0.32 vs. 7.15 +/- 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions: We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid "tone" in the brain, as found in animal models of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0256-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study / M. LONG in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 1 p. Titre : Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study Type de document : Texte imprimé et/ou numérique Auteurs : M. LONG, Auteur ; M. GHISARI, Auteur ; L. KJELDSEN, Auteur ; M. WIELSOE, Auteur ; B. NORGAARD-PEDERSEN, Auteur ; E. L. MORTENSEN, Auteur ; Morsi W. ABDALLAH, Auteur ; E. C. BONEFELD-JORGENSEN, Auteur Article en page(s) : 1 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Amniotic Fluid/*chemistry  Animals  Autism Spectrum Disorder/epidemiology/*etiology  CHO Cells  Case-Control Studies  Child  Cricetinae  Cricetulus  Endocrine Disruptors/*analysis/toxicity  Female  Humans  Infant, Newborn  Male  Metals, Heavy/*analysis/toxicity  Middle Aged  *Amniotic fluid  *Autism  *Endocrine disrupting compounds  *Receptor activity  Newborn Screening Biobank and the Danish Data Protection Agency (Record No.  2009-41-3173) as well as the Central Denmark Region Ethics Committee on Health  Research (Record No. M-20090066). Since all data were obtained retrospectively in  an anonymized manner, there was no need to obtain consent from any of the  participants.Not applicableThe authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Evidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk. Methods: In this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance. Results: PFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p = 0.042; FDR q value = 0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR = 0.100; 95% CI 0.016, 0.630; p = 0.014; FDR q value = 0.098).Testosterone level in AF weakly associated with ASD risk (adjusted OR = 1.002; 95% CI 1.000, 1.004; p = 0.05). However, after multiple comparison correction, the association was not significant (FDR q value = 0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity. Conclusions: The presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS.The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0253-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Autism spectrum disorders, endocrine disrupting compounds, and heavy metals in amniotic fluid: a case-control study [Texte imprimé et/ou numérique] / M. LONG, Auteur ; M. GHISARI, Auteur ; L. KJELDSEN, Auteur ; M. WIELSOE, Auteur ; B. NORGAARD-PEDERSEN, Auteur ; E. L. MORTENSEN, Auteur ; Morsi W. ABDALLAH, Auteur ; E. C. BONEFELD-JORGENSEN, Auteur . - 1 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 1 p. Mots-clés : Adolescent  Adult  Amniotic Fluid/*chemistry  Animals  Autism Spectrum Disorder/epidemiology/*etiology  CHO Cells  Case-Control Studies  Child  Cricetinae  Cricetulus  Endocrine Disruptors/*analysis/toxicity  Female  Humans  Infant, Newborn  Male  Metals, Heavy/*analysis/toxicity  Middle Aged  *Amniotic fluid  *Autism  *Endocrine disrupting compounds  *Receptor activity  Newborn Screening Biobank and the Danish Data Protection Agency (Record No.  2009-41-3173) as well as the Central Denmark Region Ethics Committee on Health  Research (Record No. M-20090066). Since all data were obtained retrospectively in  an anonymized manner, there was no need to obtain consent from any of the  participants.Not applicableThe authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Evidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk. Methods: In this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance. Results: PFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p = 0.042; FDR q value = 0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR = 0.100; 95% CI 0.016, 0.630; p = 0.014; FDR q value = 0.098).Testosterone level in AF weakly associated with ASD risk (adjusted OR = 1.002; 95% CI 1.000, 1.004; p = 0.05). However, after multiple comparison correction, the association was not significant (FDR q value = 0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity. Conclusions: The presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS.The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0253-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Autistic traits, resting-state connectivity, and absolute pitch in professional musicians: shared and distinct neural features / T. WENHART in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 20 p. Titre : Autistic traits, resting-state connectivity, and absolute pitch in professional musicians: shared and distinct neural features Type de document : Texte imprimé et/ou numérique Auteurs : T. WENHART, Auteur ; Richard A. I. BETHLEHEM, Auteur ; Simon BARON-COHEN, Auteur ; E. ALTENMULLER, Auteur Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Absolute pitch  Autistic traits  Brain networks  Electroencephalography  Graph theory  Musicians Index. décimale : PER Périodiques Résumé : Background: Recent studies indicate increased autistic traits in musicians with absolute pitch and a higher proportion of absolute pitch in people with autism. Theoretical accounts connect both of these with shared neural principles of local hyper- and global hypoconnectivity, enhanced perceptual functioning, and a detail-focused cognitive style. This is the first study to investigate absolute pitch proficiency, autistic traits, and brain correlates in the same study. Sample and methods: Graph theoretical analysis was conducted on resting-state (eyes closed and eyes open) EEG connectivity (wPLI, weighted phase lag index) matrices obtained from 31 absolute pitch (AP) and 33 relative pitch (RP) professional musicians. Small-worldness, global clustering coefficient, and average path length were related to autistic traits, passive (tone identification) and active (pitch adjustment) absolute pitch proficiency, and onset of musical training using Welch two-sample tests, correlations, and general linear models. Results: Analyses revealed increased path length (delta 2-4 Hz), reduced clustering (beta 13-18 Hz), reduced small-worldness (gamma 30-60 Hz), and increased autistic traits for AP compared to RP. Only clustering values (beta 13-18 Hz) were predicted by both AP proficiency and autistic traits. Post hoc single connection permutation tests among raw wPLI matrices in the beta band (13-18 Hz) revealed widely reduced interhemispheric connectivity between bilateral auditory-related electrode positions along with higher connectivity between F7-F8 and F8-P9 for AP. Pitch-naming ability and pitch adjustment ability were predicted by path length, clustering, autistic traits, and onset of musical training (for pitch adjustment) explaining 44% and 38% of variance, respectively. Conclusions: Results show both shared and distinct neural features between AP and autistic traits. Differences in the beta range were associated with higher autistic traits in the same population. In general, AP musicians exhibit a widely underconnected brain with reduced functional integration and reduced small-world property during resting state. This might be partly related to autism-specific brain connectivity, while differences in path length and small-worldness reflect other ability-specific influences. This is further evidenced for different pathways in the acquisition and development of absolute pitch, likely influenced by both genetic and environmental factors and their interaction. En ligne : http://dx.doi.org/10.1186/s13229-019-0272-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] Autistic traits, resting-state connectivity, and absolute pitch in professional musicians: shared and distinct neural features [Texte imprimé et/ou numérique] / T. WENHART, Auteur ; Richard A. I. BETHLEHEM, Auteur ; Simon BARON-COHEN, Auteur ; E. ALTENMULLER, Auteur . - 20 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 20 p. Mots-clés : Absolute pitch  Autistic traits  Brain networks  Electroencephalography  Graph theory  Musicians Index. décimale : PER Périodiques Résumé : Background: Recent studies indicate increased autistic traits in musicians with absolute pitch and a higher proportion of absolute pitch in people with autism. Theoretical accounts connect both of these with shared neural principles of local hyper- and global hypoconnectivity, enhanced perceptual functioning, and a detail-focused cognitive style. This is the first study to investigate absolute pitch proficiency, autistic traits, and brain correlates in the same study. Sample and methods: Graph theoretical analysis was conducted on resting-state (eyes closed and eyes open) EEG connectivity (wPLI, weighted phase lag index) matrices obtained from 31 absolute pitch (AP) and 33 relative pitch (RP) professional musicians. Small-worldness, global clustering coefficient, and average path length were related to autistic traits, passive (tone identification) and active (pitch adjustment) absolute pitch proficiency, and onset of musical training using Welch two-sample tests, correlations, and general linear models. Results: Analyses revealed increased path length (delta 2-4 Hz), reduced clustering (beta 13-18 Hz), reduced small-worldness (gamma 30-60 Hz), and increased autistic traits for AP compared to RP. Only clustering values (beta 13-18 Hz) were predicted by both AP proficiency and autistic traits. Post hoc single connection permutation tests among raw wPLI matrices in the beta band (13-18 Hz) revealed widely reduced interhemispheric connectivity between bilateral auditory-related electrode positions along with higher connectivity between F7-F8 and F8-P9 for AP. Pitch-naming ability and pitch adjustment ability were predicted by path length, clustering, autistic traits, and onset of musical training (for pitch adjustment) explaining 44% and 38% of variance, respectively. Conclusions: Results show both shared and distinct neural features between AP and autistic traits. Differences in the beta range were associated with higher autistic traits in the same population. In general, AP musicians exhibit a widely underconnected brain with reduced functional integration and reduced small-world property during resting state. This might be partly related to autism-specific brain connectivity, while differences in path length and small-worldness reflect other ability-specific influences. This is further evidenced for different pathways in the acquisition and development of absolute pitch, likely influenced by both genetic and environmental factors and their interaction. En ligne : http://dx.doi.org/10.1186/s13229-019-0272-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features / E. K. BAKER in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 21 p. Titre : Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features Type de document : Texte imprimé et/ou numérique Auteurs : E. K. BAKER, Auteur ; M. ARPONE, Auteur ; S. M. ALIAGA, Auteur ; L. BRETHERTON, Auteur ; C. M. KRAAN, Auteur ; M. BUI, Auteur ; H. R. SLATER, Auteur ; L. LING, Auteur ; D. FRANCIS, Auteur ; M. F. HUNTER, Auteur ; J. ELLIOTT, Auteur ; C. ROGERS, Auteur ; M. FIELD, Auteur ; J. COHEN, Auteur ; Kim CORNISH, Auteur ; L. SANTA MARIA, Auteur ; V. FAUNDES, Auteur ; B. CUROTTO, Auteur ; P. MORALES, Auteur ; C. TRIGO, Auteur ; I. SALAS, Auteur ; A. M. ALLIENDE, Auteur ; D. J. AMOR, Auteur ; D. E. GODLER, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Mots-clés : Autism  FMR1 mRNA  Fragile X syndrome  Intellectual disability  Mosaicism Index. décimale : PER Périodiques Résumé : Background: Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the FMR1 product (FMRP), mosaicism for active and inactive FMR1 alleles, including alleles termed premutation (PM: 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM: >/= 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic. This study determined if complete FMR1 mRNA silencing from FM alleles and/or levels of FMR1 mRNA (if present) in blood are associated with intellectual functioning and autism features in FXS. Methods: The study cohort included 98 participants (70.4% male) with FXS (FM-only and PM/FM mosaic) aged 1-43 years. A control group of 14 females were used to establish control FMR1 mRNA reference range. Intellectual functioning and autism features were assessed using the Mullen Scales of Early Learning or an age-appropriate Wechsler Scale and the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2), respectively. FMR1 mRNA was analysed in venous blood collected at the time of assessments, using the real-time PCR relative standard curve method. Results: Females with FXS had significantly higher levels of FMR1 mRNA (p < 0.001) than males. FMR1 mRNA levels were positively associated with age (p < 0.001), but not with intellectual functioning and autistic features in females. FM-only males (aged < 19 years) expressing FM FMR1 mRNA had significantly higher ADOS calibrated severity scores compared to FM-only males with completely silenced FMR1 (p = 0.011). However, there were no significant differences between these subgroups on intellectual functioning. In contrast, decreased levels of FMR1 mRNA were associated with decreased intellectual functioning in FXS males (p = 0.029), but not autism features, when combined with the PM/FM mosaic group. Conclusion: Incomplete silencing of toxic FM RNA may be associated with autistic features, but not intellectual functioning in FXS males. While decreased levels of mRNA may be more predictive of intellectual functioning than autism features. If confirmed in future studies, these findings may have implications for patient stratification, outcome measure development, and design of clinical and pre-clinical trials in FXS. En ligne : http://dx.doi.org/10.1186/s13229-019-0271-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features [Texte imprimé et/ou numérique] / E. K. BAKER, Auteur ; M. ARPONE, Auteur ; S. M. ALIAGA, Auteur ; L. BRETHERTON, Auteur ; C. M. KRAAN, Auteur ; M. BUI, Auteur ; H. R. SLATER, Auteur ; L. LING, Auteur ; D. FRANCIS, Auteur ; M. F. HUNTER, Auteur ; J. ELLIOTT, Auteur ; C. ROGERS, Auteur ; M. FIELD, Auteur ; J. COHEN, Auteur ; Kim CORNISH, Auteur ; L. SANTA MARIA, Auteur ; V. FAUNDES, Auteur ; B. CUROTTO, Auteur ; P. MORALES, Auteur ; C. TRIGO, Auteur ; I. SALAS, Auteur ; A. M. ALLIENDE, Auteur ; D. J. AMOR, Auteur ; D. E. GODLER, Auteur . - 21 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 21 p. Mots-clés : Autism  FMR1 mRNA  Fragile X syndrome  Intellectual disability  Mosaicism Index. décimale : PER Périodiques Résumé : Background: Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the FMR1 product (FMRP), mosaicism for active and inactive FMR1 alleles, including alleles termed premutation (PM: 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM: >/= 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic. This study determined if complete FMR1 mRNA silencing from FM alleles and/or levels of FMR1 mRNA (if present) in blood are associated with intellectual functioning and autism features in FXS. Methods: The study cohort included 98 participants (70.4% male) with FXS (FM-only and PM/FM mosaic) aged 1-43 years. A control group of 14 females were used to establish control FMR1 mRNA reference range. Intellectual functioning and autism features were assessed using the Mullen Scales of Early Learning or an age-appropriate Wechsler Scale and the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2), respectively. FMR1 mRNA was analysed in venous blood collected at the time of assessments, using the real-time PCR relative standard curve method. Results: Females with FXS had significantly higher levels of FMR1 mRNA (p < 0.001) than males. FMR1 mRNA levels were positively associated with age (p < 0.001), but not with intellectual functioning and autistic features in females. FM-only males (aged < 19 years) expressing FM FMR1 mRNA had significantly higher ADOS calibrated severity scores compared to FM-only males with completely silenced FMR1 (p = 0.011). However, there were no significant differences between these subgroups on intellectual functioning. In contrast, decreased levels of FMR1 mRNA were associated with decreased intellectual functioning in FXS males (p = 0.029), but not autism features, when combined with the PM/FM mosaic group. Conclusion: Incomplete silencing of toxic FM RNA may be associated with autistic features, but not intellectual functioning in FXS males. While decreased levels of mRNA may be more predictive of intellectual functioning than autism features. If confirmed in future studies, these findings may have implications for patient stratification, outcome measure development, and design of clinical and pre-clinical trials in FXS. En ligne : http://dx.doi.org/10.1186/s13229-019-0271-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

Retinal alterations in a pre-clinical model of an autism spectrum disorder / E. M. GUIMARAES-SOUZA in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 19 p. Titre : Retinal alterations in a pre-clinical model of an autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : E. M. GUIMARAES-SOUZA, Auteur ; C. JOSELEVITCH, Auteur ; L. R. G. BRITTO, Auteur ; S. CHIAVEGATTO, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Adolescence  Autism  gaba  Glutamate  Neurodevelopment  Retina  Valproate  Vision Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Disturbances in glutamatergic and GABAergic signaling that lead to synaptic changes and alter the balance between excitation and inhibition in the developing brain are consistently found in ASD. One of the hallmarks of these disorders is hypersensitivity to sensory stimuli; however, little is known about its underlying causes. Since the retina is the part of the CNS that converts light into a neuronal signal, we set out to study how it is affected in adolescent mice prenatally exposed to valproic acid (VPA), a useful tool to study ASD endophenotypes. Methods: Pregnant female mice received VPA (600 mg/kg, ip) or saline at gestational day 11. Their male adolescent pups (P29-35) were behaviorally tested for anxiety and social interaction. Proteins known to be related with ASD were quantified and visualized in their retinas by immunoassays, and retinal function was assessed by full-field scotopic electroretinograms (ERGs). Results: Early adolescent mice prenatally exposed to VPA displayed impaired social interest and increased anxiety-like behaviors consistent with an ASD phenotype. The expression of GABA, GAD, synapsin-1, and FMRP proteins were reduced in their retinas, while mGluR5 was increased. The a-wave amplitudes of VPA-exposed were smaller than those of CTR animals, whereas the b-wave and oscillatory potentials were normal. Conclusions: This study establishes that adolescent male mice of the VPA-induced ASD model have alterations in retinal function and protein expression compatible with those found in several brain areas of other autism models. These results support the view that synaptic disturbances with excitatory/inhibitory imbalance early in life are associated with ASD and point to the retina as a window to understand their subjacent mechanisms. En ligne : http://dx.doi.org/10.1186/s13229-019-0270-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] Retinal alterations in a pre-clinical model of an autism spectrum disorder [Texte imprimé et/ou numérique] / E. M. GUIMARAES-SOUZA, Auteur ; C. JOSELEVITCH, Auteur ; L. R. G. BRITTO, Auteur ; S. CHIAVEGATTO, Auteur . - 19 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 19 p. Mots-clés : Adolescence  Autism  gaba  Glutamate  Neurodevelopment  Retina  Valproate  Vision Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Disturbances in glutamatergic and GABAergic signaling that lead to synaptic changes and alter the balance between excitation and inhibition in the developing brain are consistently found in ASD. One of the hallmarks of these disorders is hypersensitivity to sensory stimuli; however, little is known about its underlying causes. Since the retina is the part of the CNS that converts light into a neuronal signal, we set out to study how it is affected in adolescent mice prenatally exposed to valproic acid (VPA), a useful tool to study ASD endophenotypes. Methods: Pregnant female mice received VPA (600 mg/kg, ip) or saline at gestational day 11. Their male adolescent pups (P29-35) were behaviorally tested for anxiety and social interaction. Proteins known to be related with ASD were quantified and visualized in their retinas by immunoassays, and retinal function was assessed by full-field scotopic electroretinograms (ERGs). Results: Early adolescent mice prenatally exposed to VPA displayed impaired social interest and increased anxiety-like behaviors consistent with an ASD phenotype. The expression of GABA, GAD, synapsin-1, and FMRP proteins were reduced in their retinas, while mGluR5 was increased. The a-wave amplitudes of VPA-exposed were smaller than those of CTR animals, whereas the b-wave and oscillatory potentials were normal. Conclusions: This study establishes that adolescent male mice of the VPA-induced ASD model have alterations in retinal function and protein expression compatible with those found in several brain areas of other autism models. These results support the view that synaptic disturbances with excitatory/inhibitory imbalance early in life are associated with ASD and point to the retina as a window to understand their subjacent mechanisms. En ligne : http://dx.doi.org/10.1186/s13229-019-0270-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

A "choice", an "addiction", a way "out of the lost": exploring self-injury in autistic people without intellectual disability / R. L. MOSELEY in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 18 p. Titre : A "choice", an "addiction", a way "out of the lost": exploring self-injury in autistic people without intellectual disability Type de document : Texte imprimé et/ou numérique Auteurs : R. L. MOSELEY, Auteur ; N. J. GREGORY, Auteur ; P. SMITH, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 18 p. Langues : Anglais (eng) Mots-clés : Alexithymia  Autism  Qualitative  Self-harm  Self-injury  Sensory differences  Suicidality Index. décimale : PER Périodiques Résumé : Background: Non-suicidal self-injury (NSSI) describes a phenomenon where individuals inflict deliberate pain and tissue damage to their bodies. Self-injurious behaviour is especially prevalent across the autism spectrum, but little is understood about the features and functions of self-injury for autistic individuals without intellectual disability, or about the risk factors that might be valuable for clinical usage in this group. Methods: One hundred and three autistic adults who responded to an online advertisement were classified as current, historic or non-self-harmers in accordance with responses to the Non-Suicidal Self-Injury Assessment Tool (NSSI-AT). Multinomial regression aimed to predict categorisation of participants in accordance with scores on tests of autistic traits, alexithymia, depression, anxiety, mentalising and sensory sensitivity. Linear regression examined relationships between these predictors and the range, frequency, lifetime occurrence and functional purposes of NSSI. Qualitative analysis explored the therapeutic interventions that participants had found helpful, and what they wished people understood about self-injury. Results: Current, historic and non-self-harming participants did not differ in age, age at diagnosis, male-to-female ratio, level of employment or education (the majority qualified to at least degree level). The most common function of NSSI was the regulation of low-energy affective states (depression, dissociation), followed by the regulation of high-energy states such as anger and anxiety. Alexithymia significantly predicted the categorisation of participants as current, historic or non-self-harmers, and predicted use of NSSI for regulating high-energy states and communicating distress to others. Depression, anxiety and sensory-sensitivity also differentiated participant groups, and sensory differences also predicted the range of bodily areas targeted, lifetime incidence and frequency of NSSI. Sensory differences, difficulty expressing and identifying emotions also emerged as problematic in the qualitative analysis, where participants expressed the need for compassion, patience, non-judgement and the need to recognise diversity between self-harmers, with some participants perceiving NSSI as a practical, non-problematic coping strategy. Conclusions: Alexithymia, depression, anxiety and sensory differences may place some autistic individuals at especial risk of self-injury. Investigating the involvement of these variables and their utility for identification and treatment is of high importance, and the voices of participants offer guidance to practitioners confronted with NSSI in their autistic clients. En ligne : http://dx.doi.org/10.1186/s13229-019-0267-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] A "choice", an "addiction", a way "out of the lost": exploring self-injury in autistic people without intellectual disability [Texte imprimé et/ou numérique] / R. L. MOSELEY, Auteur ; N. J. GREGORY, Auteur ; P. SMITH, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur . - 18 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 18 p. Mots-clés : Alexithymia  Autism  Qualitative  Self-harm  Self-injury  Sensory differences  Suicidality Index. décimale : PER Périodiques Résumé : Background: Non-suicidal self-injury (NSSI) describes a phenomenon where individuals inflict deliberate pain and tissue damage to their bodies. Self-injurious behaviour is especially prevalent across the autism spectrum, but little is understood about the features and functions of self-injury for autistic individuals without intellectual disability, or about the risk factors that might be valuable for clinical usage in this group. Methods: One hundred and three autistic adults who responded to an online advertisement were classified as current, historic or non-self-harmers in accordance with responses to the Non-Suicidal Self-Injury Assessment Tool (NSSI-AT). Multinomial regression aimed to predict categorisation of participants in accordance with scores on tests of autistic traits, alexithymia, depression, anxiety, mentalising and sensory sensitivity. Linear regression examined relationships between these predictors and the range, frequency, lifetime occurrence and functional purposes of NSSI. Qualitative analysis explored the therapeutic interventions that participants had found helpful, and what they wished people understood about self-injury. Results: Current, historic and non-self-harming participants did not differ in age, age at diagnosis, male-to-female ratio, level of employment or education (the majority qualified to at least degree level). The most common function of NSSI was the regulation of low-energy affective states (depression, dissociation), followed by the regulation of high-energy states such as anger and anxiety. Alexithymia significantly predicted the categorisation of participants as current, historic or non-self-harmers, and predicted use of NSSI for regulating high-energy states and communicating distress to others. Depression, anxiety and sensory-sensitivity also differentiated participant groups, and sensory differences also predicted the range of bodily areas targeted, lifetime incidence and frequency of NSSI. Sensory differences, difficulty expressing and identifying emotions also emerged as problematic in the qualitative analysis, where participants expressed the need for compassion, patience, non-judgement and the need to recognise diversity between self-harmers, with some participants perceiving NSSI as a practical, non-problematic coping strategy. Conclusions: Alexithymia, depression, anxiety and sensory differences may place some autistic individuals at especial risk of self-injury. Investigating the involvement of these variables and their utility for identification and treatment is of high importance, and the voices of participants offer guidance to practitioners confronted with NSSI in their autistic clients. En ligne : http://dx.doi.org/10.1186/s13229-019-0267-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer / J. FORES-MARTOS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 17 p. Titre : Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer Type de document : Texte imprimé et/ou numérique Auteurs : J. FORES-MARTOS, Auteur ; F. CATALA-LOPEZ, Auteur ; J. SANCHEZ-VALLE, Auteur ; K. IBANEZ, Auteur ; H. TEJERO, Auteur ; H. PALMA-GUDIEL, Auteur ; J. CLIMENT, Auteur ; V. PANCALDI, Auteur ; L. FANANAS, Auteur ; C. ARANGO, Auteur ; Mara PARELLADA, Auteur ; A. BAUDOT, Auteur ; D. VOGT, Auteur ; J. L. RUBENSTEIN, Auteur ; A. VALENCIA, Auteur ; R. TABARES-SEISDEDOS, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : asd  Autism  Cancer  Comorbidity  Gene expression  Meta-analysis  Multimorbidity  Transcriptome Index. décimale : PER Périodiques Résumé : Background: Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Methods: Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer types obtained by differential expression meta-analysis and report gene, pathway, and drug set-based overlaps between them. Results: Four cancer types (brain, thyroid, kidney, and pancreatic cancers) presented a significant overlap in gene expression deregulations in the same direction as ASD whereas two cancer types (lung and prostate cancers) showed differential expression profiles significantly deregulated in the opposite direction from ASD. Functional enrichment and LINCS L1000 based drug set enrichment analyses revealed the implication of several biological processes and pathways that were affected jointly in both diseases, including impairments of the immune system, and impairments in oxidative phosphorylation and ATP synthesis among others. Our data also suggest that brain and kidney cancer have patterns of transcriptomic dysregulation in the PI3K/AKT/MTOR axis that are similar to those found in ASD. Conclusions: Comparisons of ASD and cancer differential gene expression meta-analysis results suggest that brain, kidney, thyroid, and pancreatic cancers are candidates for direct comorbid associations with ASD. On the other hand, lung and prostate cancers are candidates for inverse comorbid associations with ASD. Joint perturbations in a set of specific biological processes underlie these associations which include several pathways previously implicated in both cancer and ASD encompassing immune system alterations, impairments of energy metabolism, cell cycle, and signaling through PI3K and G protein-coupled receptors among others. These findings could help to explain epidemiological observations pointing towards direct and inverse comorbid associations between ASD and specific cancer types and depict a complex scenario regarding the molecular patterns of association between ASD and cancer. En ligne : http://dx.doi.org/10.1186/s13229-019-0262-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer [Texte imprimé et/ou numérique] / J. FORES-MARTOS, Auteur ; F. CATALA-LOPEZ, Auteur ; J. SANCHEZ-VALLE, Auteur ; K. IBANEZ, Auteur ; H. TEJERO, Auteur ; H. PALMA-GUDIEL, Auteur ; J. CLIMENT, Auteur ; V. PANCALDI, Auteur ; L. FANANAS, Auteur ; C. ARANGO, Auteur ; Mara PARELLADA, Auteur ; A. BAUDOT, Auteur ; D. VOGT, Auteur ; J. L. RUBENSTEIN, Auteur ; A. VALENCIA, Auteur ; R. TABARES-SEISDEDOS, Auteur . - 17 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 17 p. Mots-clés : asd  Autism  Cancer  Comorbidity  Gene expression  Meta-analysis  Multimorbidity  Transcriptome Index. décimale : PER Périodiques Résumé : Background: Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Methods: Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer types obtained by differential expression meta-analysis and report gene, pathway, and drug set-based overlaps between them. Results: Four cancer types (brain, thyroid, kidney, and pancreatic cancers) presented a significant overlap in gene expression deregulations in the same direction as ASD whereas two cancer types (lung and prostate cancers) showed differential expression profiles significantly deregulated in the opposite direction from ASD. Functional enrichment and LINCS L1000 based drug set enrichment analyses revealed the implication of several biological processes and pathways that were affected jointly in both diseases, including impairments of the immune system, and impairments in oxidative phosphorylation and ATP synthesis among others. Our data also suggest that brain and kidney cancer have patterns of transcriptomic dysregulation in the PI3K/AKT/MTOR axis that are similar to those found in ASD. Conclusions: Comparisons of ASD and cancer differential gene expression meta-analysis results suggest that brain, kidney, thyroid, and pancreatic cancers are candidates for direct comorbid associations with ASD. On the other hand, lung and prostate cancers are candidates for inverse comorbid associations with ASD. Joint perturbations in a set of specific biological processes underlie these associations which include several pathways previously implicated in both cancer and ASD encompassing immune system alterations, impairments of energy metabolism, cell cycle, and signaling through PI3K and G protein-coupled receptors among others. These findings could help to explain epidemiological observations pointing towards direct and inverse comorbid associations between ASD and specific cancer types and depict a complex scenario regarding the molecular patterns of association between ASD and cancer. En ligne : http://dx.doi.org/10.1186/s13229-019-0262-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

The role of gender in the perception of autism symptom severity and future behavioral development / Philippine GEELHAND in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 16 p. Titre : The role of gender in the perception of autism symptom severity and future behavioral development Type de document : Texte imprimé et/ou numérique Auteurs : Philippine GEELHAND, Auteur ; P. BERNARD, Auteur ; O. KLEIN, Auteur ; B. VAN TIEL, Auteur ; M. KISSINE, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Mots-clés : Adolescence  Caregiver  Concern  Gender bias  Sex ratio  Symptom severity Index. décimale : PER Périodiques Résumé : Background: Increasing attention is being paid to the higher prevalence of boys with Autism Spectrum Disorder (ASD) and to the implications of this ratio discrepancy on our understanding of autism in girls. One recent avenue of research has focused on caregiver's concern, suggesting that autism might present differently in boys and girls. One unexplored factor related to concerns on child development is whether socio-cultural factors such as gender-related expectations influence the evaluation of symptom severity and predictions about future behavioral development. Methods: The latter concerns were the focus of the present study and were explored by investigating laypeople's judgment of the severity of autism symptoms using an online parent role-playing paradigm, in which participants were asked to rate vignettes depicting the behaviors of a child in different everyday life scenarios. The child's gender and the severity of ASD symptoms were manipulated to examine the effect of gender on the perception of symptom severity. Results: Results suggest that there are no gender differences in perceived symptom severity and associated degree of concern for 5-year-old boys and girls but that there is a gender difference in perceived future atypicality at 15 years old, with boys being rated as more likely to be perceived as atypical by their peers at that age than girls. Conclusions: Investigating parent's cognition about their child's future behavioral development can provide additional information regarding delayed diagnosis of autistic girls. En ligne : http://dx.doi.org/10.1186/s13229-019-0266-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] The role of gender in the perception of autism symptom severity and future behavioral development [Texte imprimé et/ou numérique] / Philippine GEELHAND, Auteur ; P. BERNARD, Auteur ; O. KLEIN, Auteur ; B. VAN TIEL, Auteur ; M. KISSINE, Auteur . - 16 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 16 p. Mots-clés : Adolescence  Caregiver  Concern  Gender bias  Sex ratio  Symptom severity Index. décimale : PER Périodiques Résumé : Background: Increasing attention is being paid to the higher prevalence of boys with Autism Spectrum Disorder (ASD) and to the implications of this ratio discrepancy on our understanding of autism in girls. One recent avenue of research has focused on caregiver's concern, suggesting that autism might present differently in boys and girls. One unexplored factor related to concerns on child development is whether socio-cultural factors such as gender-related expectations influence the evaluation of symptom severity and predictions about future behavioral development. Methods: The latter concerns were the focus of the present study and were explored by investigating laypeople's judgment of the severity of autism symptoms using an online parent role-playing paradigm, in which participants were asked to rate vignettes depicting the behaviors of a child in different everyday life scenarios. The child's gender and the severity of ASD symptoms were manipulated to examine the effect of gender on the perception of symptom severity. Results: Results suggest that there are no gender differences in perceived symptom severity and associated degree of concern for 5-year-old boys and girls but that there is a gender difference in perceived future atypicality at 15 years old, with boys being rated as more likely to be perceived as atypical by their peers at that age than girls. Conclusions: Investigating parent's cognition about their child's future behavioral development can provide additional information regarding delayed diagnosis of autistic girls. En ligne : http://dx.doi.org/10.1186/s13229-019-0266-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

Scn2a haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity / T. TATSUKAWA in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 15 p. Titre : Scn2a haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity Type de document : Texte imprimé et/ou numérique Auteurs : T. TATSUKAWA, Auteur ; M. RAVEAU, Auteur ; I. OGIWARA, Auteur ; S. HATTORI, Auteur ; H. MIYAMOTO, Auteur ; E. MAZAKI, Auteur ; S. ITOHARA, Auteur ; T. MIYAKAWA, Auteur ; M. MONTAL, Auteur ; K. YAMAKAWA, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : AMPA receptor  Autism  Schizophrenia  Scn2a Index. décimale : PER Périodiques Résumé : Background: Mutations of the SCN2A gene encoding a voltage-gated sodium channel alpha-II subunit Nav1.2 are associated with neurological disorders such as epilepsy, autism spectrum disorders, intellectual disability, and schizophrenia. However, causal relationships and pathogenic mechanisms underlying these neurological defects, especially social and psychiatric features, remain to be elucidated. Methods: We investigated the behavior of mice with a conventional or conditional deletion of Scn2a in a comprehensive test battery including open field, elevated plus maze, light-dark box, three chambers, social dominance tube, resident-intruder, ultrasonic vocalization, and fear conditioning tests. We further monitored the effects of the positive allosteric modulator of AMPA receptors CX516 on these model mice. Results: Conventional heterozygous Scn2a knockout mice (Scn2a (KO/+)) displayed novelty-induced exploratory hyperactivity and increased rearing. The increased vertical activity was reproduced by heterozygous inactivation of Scn2a in dorsal-telencephalic excitatory neurons but not in inhibitory neurons. Moreover, these phenotypes were rescued by treating Scn2a (KO/+) mice with CX516. Additionally, Scn2a (KO/+) mice displayed mild social behavior impairment, enhanced fear conditioning, and deficient fear extinction. Neuronal activity was intensified in the medial prefrontal cortex of Scn2a (KO/+) mice, with an increase in the gamma band. Conclusions: Scn2a (KO/+) mice exhibit a spectrum of phenotypes commonly observed in models of schizophrenia and autism spectrum disorder. Treatment with the CX516 ampakine, which ameliorates hyperactivity in these mice, could be a potential therapeutic strategy to rescue some of the disease phenotypes. En ligne : http://dx.doi.org/10.1186/s13229-019-0265-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] Scn2a haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity [Texte imprimé et/ou numérique] / T. TATSUKAWA, Auteur ; M. RAVEAU, Auteur ; I. OGIWARA, Auteur ; S. HATTORI, Auteur ; H. MIYAMOTO, Auteur ; E. MAZAKI, Auteur ; S. ITOHARA, Auteur ; T. MIYAKAWA, Auteur ; M. MONTAL, Auteur ; K. YAMAKAWA, Auteur . - 15 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 15 p. Mots-clés : AMPA receptor  Autism  Schizophrenia  Scn2a Index. décimale : PER Périodiques Résumé : Background: Mutations of the SCN2A gene encoding a voltage-gated sodium channel alpha-II subunit Nav1.2 are associated with neurological disorders such as epilepsy, autism spectrum disorders, intellectual disability, and schizophrenia. However, causal relationships and pathogenic mechanisms underlying these neurological defects, especially social and psychiatric features, remain to be elucidated. Methods: We investigated the behavior of mice with a conventional or conditional deletion of Scn2a in a comprehensive test battery including open field, elevated plus maze, light-dark box, three chambers, social dominance tube, resident-intruder, ultrasonic vocalization, and fear conditioning tests. We further monitored the effects of the positive allosteric modulator of AMPA receptors CX516 on these model mice. Results: Conventional heterozygous Scn2a knockout mice (Scn2a (KO/+)) displayed novelty-induced exploratory hyperactivity and increased rearing. The increased vertical activity was reproduced by heterozygous inactivation of Scn2a in dorsal-telencephalic excitatory neurons but not in inhibitory neurons. Moreover, these phenotypes were rescued by treating Scn2a (KO/+) mice with CX516. Additionally, Scn2a (KO/+) mice displayed mild social behavior impairment, enhanced fear conditioning, and deficient fear extinction. Neuronal activity was intensified in the medial prefrontal cortex of Scn2a (KO/+) mice, with an increase in the gamma band. Conclusions: Scn2a (KO/+) mice exhibit a spectrum of phenotypes commonly observed in models of schizophrenia and autism spectrum disorder. Treatment with the CX516 ampakine, which ameliorates hyperactivity in these mice, could be a potential therapeutic strategy to rescue some of the disease phenotypes. En ligne : http://dx.doi.org/10.1186/s13229-019-0265-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

Linguistic markers of autism in girls: evidence of a "blended phenotype" during storytelling / J. BOORSE in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 14 p. Titre : Linguistic markers of autism in girls: evidence of a "blended phenotype" during storytelling Type de document : Texte imprimé et/ou numérique Auteurs : J. BOORSE, Auteur ; M. COLA, Auteur ; S. PLATE, Auteur ; L. YANKOWITZ, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Mentalizing  Narratives  Natural language processing  Sex differences  Social cognition  Storytelling  Word choice Index. décimale : PER Périodiques Résumé : Background: Narrative abilities are linked to social impairment in autism spectrum disorder (ASD), such that reductions in words about cognitive processes (e.g., think, know) are thought to reflect underlying deficits in social cognition, including Theory of Mind. However, research suggests that typically developing (TD) boys and girls tell narratives in sex-specific ways, including differential reliance on cognitive process words. Given that most studies of narration in ASD have been conducted in predominantly male samples, it is possible that prior results showing reduced cognitive processing language in ASD may not generalize to autistic girls. To answer this question, we measured the relative frequency of two kinds of words in stories told by autistic girls and boys: nouns (words that indicate object-oriented storytelling) and cognitive process words (words like think and know that indicate mentalizing or attention to other peoples' internal states). Methods: One hundred two verbally fluent school-aged children [girls with ASD (N = 21) and TD (N = 19), and boys with ASD (N = 41) and TD (N = 21)] were matched on age, IQ, and maternal education. Children told a story from a sequence of pictures, and word frequencies (nouns, cognitive process words) were compared. Results: Autistic children of both sexes consistently produced a greater number of nouns than TD controls, indicating object-focused storytelling. There were no sex differences in cognitive process word use in the TD group, but autistic girls produced significantly more cognitive process words than autistic boys, despite comparable autism symptom severity. Thus, autistic girls showed a unique narrative profile that overlapped with autistic boys and typical girls/boys. Noun use correlated significantly with parent reports of social symptom severity in all groups, but cognitive process word use correlated with social ability in boys only. Conclusion: This study extends prior research on autistic children's storytelling by measuring sex differences in the narratives of a relatively large, well-matched sample of children with and without ASD. Importantly, prior research showing that autistic children use fewer cognitive process words is true for boys only, while object-focused language is a sex-neutral linguistic marker of ASD. These findings suggest that sex-sensitive screening and diagnostic methods-preferably using objective metrics like natural language processing-may be helpful for identifying autistic girls, and could guide the development of future personalized treatment strategies. En ligne : http://dx.doi.org/10.1186/s13229-019-0268-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] Linguistic markers of autism in girls: evidence of a "blended phenotype" during storytelling [Texte imprimé et/ou numérique] / J. BOORSE, Auteur ; M. COLA, Auteur ; S. PLATE, Auteur ; L. YANKOWITZ, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur . - 14 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 14 p. Mots-clés : Autism spectrum disorder  Mentalizing  Narratives  Natural language processing  Sex differences  Social cognition  Storytelling  Word choice Index. décimale : PER Périodiques Résumé : Background: Narrative abilities are linked to social impairment in autism spectrum disorder (ASD), such that reductions in words about cognitive processes (e.g., think, know) are thought to reflect underlying deficits in social cognition, including Theory of Mind. However, research suggests that typically developing (TD) boys and girls tell narratives in sex-specific ways, including differential reliance on cognitive process words. Given that most studies of narration in ASD have been conducted in predominantly male samples, it is possible that prior results showing reduced cognitive processing language in ASD may not generalize to autistic girls. To answer this question, we measured the relative frequency of two kinds of words in stories told by autistic girls and boys: nouns (words that indicate object-oriented storytelling) and cognitive process words (words like think and know that indicate mentalizing or attention to other peoples' internal states). Methods: One hundred two verbally fluent school-aged children [girls with ASD (N = 21) and TD (N = 19), and boys with ASD (N = 41) and TD (N = 21)] were matched on age, IQ, and maternal education. Children told a story from a sequence of pictures, and word frequencies (nouns, cognitive process words) were compared. Results: Autistic children of both sexes consistently produced a greater number of nouns than TD controls, indicating object-focused storytelling. There were no sex differences in cognitive process word use in the TD group, but autistic girls produced significantly more cognitive process words than autistic boys, despite comparable autism symptom severity. Thus, autistic girls showed a unique narrative profile that overlapped with autistic boys and typical girls/boys. Noun use correlated significantly with parent reports of social symptom severity in all groups, but cognitive process word use correlated with social ability in boys only. Conclusion: This study extends prior research on autistic children's storytelling by measuring sex differences in the narratives of a relatively large, well-matched sample of children with and without ASD. Importantly, prior research showing that autistic children use fewer cognitive process words is true for boys only, while object-focused language is a sex-neutral linguistic marker of ASD. These findings suggest that sex-sensitive screening and diagnostic methods-preferably using objective metrics like natural language processing-may be helpful for identifying autistic girls, and could guide the development of future personalized treatment strategies. En ligne : http://dx.doi.org/10.1186/s13229-019-0268-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

Autistic traits in adults who have attempted suicide / G. RICHARDS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 26p. Titre : Autistic traits in adults who have attempted suicide Type de document : Texte imprimé et/ou numérique Auteurs : G. RICHARDS, Auteur ; R. KENNY, Auteur ; S. GRIFFITHS, Auteur ; Carrie ALLISON, Auteur ; D. MOSSE, Auteur ; R. HOLT, Auteur ; R. C. O'CONNOR, Auteur ; Sarah A. CASSIDY, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 26p. Langues : Anglais (eng) Mots-clés : Asc  Asd  Asperger syndrome  Autism  Autism spectrum  Autistic traits  Depression  Mental health  Suicidality  Suicide Index. décimale : PER Périodiques Résumé : Background: An emerging literature suggests that autistic adults are at increased risk of experiencing suicidal thoughts, making suicidal plans and attempts, and dying by suicide. However, few studies have investigated whether autistic traits are related to suicidal behaviour. The current study examined autistic traits in a sample of adults who reported at least one suicide attempt. Methods: An online questionnaire was advertised between June and September 2017 on suicide prevention websites, research databases, and social media. Participants reported whether they had ever attempted suicide (yes/no), and if so, how many times they had attempted (once/more than once). They also reported diagnosed and suspected mental health or neurodevelopmental conditions, and completed the Autism Spectrum Quotient (AQ). Two hundred forty-five adults accessed the survey; 132 reported having attempted suicide and also completed the AQ. It was hypothesised that AQ total scores and subscale scores would be higher in adults who had attempted suicide more than once compared to adults who had attempted once. These hypotheses were tested using an independent samples t test, Mann-Whitney U tests, and binary logistic regression. Results: Most participants were female (83.3%, male = 12.9%, other = 3.8%), and ages ranged from 18 to 65 (median = 36.00; IQR = 19.00). Total AQ scores, as well as communication and imagination subscale scores were significantly higher in adults who had attempted suicide more than once compared to adults who had attempted suicide once. Even after removing participants with diagnosed or suspected autism (n = 34), 40.6% had an AQ score indicative of clinical concern (>/= 26). Conclusions: The findings suggest that high levels of autistic traits may frequently be present in adults who have attempted suicide, and that AQ scores are higher in those with a history of more than one suicide attempt. It may be possible to better identify suicide risk by screening autistic adults with mental health conditions for suicidal thoughts and behaviours, and by screening people with suicidal thoughts and/or behaviours for autism. En ligne : http://dx.doi.org/10.1186/s13229-019-0274-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 [article] Autistic traits in adults who have attempted suicide [Texte imprimé et/ou numérique] / G. RICHARDS, Auteur ; R. KENNY, Auteur ; S. GRIFFITHS, Auteur ; Carrie ALLISON, Auteur ; D. MOSSE, Auteur ; R. HOLT, Auteur ; R. C. O'CONNOR, Auteur ; Sarah A. CASSIDY, Auteur ; Simon BARON-COHEN, Auteur . - 26p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 26p. Mots-clés : Asc  Asd  Asperger syndrome  Autism  Autism spectrum  Autistic traits  Depression  Mental health  Suicidality  Suicide Index. décimale : PER Périodiques Résumé : Background: An emerging literature suggests that autistic adults are at increased risk of experiencing suicidal thoughts, making suicidal plans and attempts, and dying by suicide. However, few studies have investigated whether autistic traits are related to suicidal behaviour. The current study examined autistic traits in a sample of adults who reported at least one suicide attempt. Methods: An online questionnaire was advertised between June and September 2017 on suicide prevention websites, research databases, and social media. Participants reported whether they had ever attempted suicide (yes/no), and if so, how many times they had attempted (once/more than once). They also reported diagnosed and suspected mental health or neurodevelopmental conditions, and completed the Autism Spectrum Quotient (AQ). Two hundred forty-five adults accessed the survey; 132 reported having attempted suicide and also completed the AQ. It was hypothesised that AQ total scores and subscale scores would be higher in adults who had attempted suicide more than once compared to adults who had attempted once. These hypotheses were tested using an independent samples t test, Mann-Whitney U tests, and binary logistic regression. Results: Most participants were female (83.3%, male = 12.9%, other = 3.8%), and ages ranged from 18 to 65 (median = 36.00; IQR = 19.00). Total AQ scores, as well as communication and imagination subscale scores were significantly higher in adults who had attempted suicide more than once compared to adults who had attempted suicide once. Even after removing participants with diagnosed or suspected autism (n = 34), 40.6% had an AQ score indicative of clinical concern (>/= 26). Conclusions: The findings suggest that high levels of autistic traits may frequently be present in adults who have attempted suicide, and that AQ scores are higher in those with a history of more than one suicide attempt. It may be possible to better identify suicide risk by screening autistic adults with mental health conditions for suicidal thoughts and behaviours, and by screening people with suicidal thoughts and/or behaviours for autism. En ligne : http://dx.doi.org/10.1186/s13229-019-0274-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402

CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes / C. FRICANO-KUGLER in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 25p. Titre : CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : C. FRICANO-KUGLER, Auteur ; A. GORDON, Auteur ; G. SHIN, Auteur ; K. GAO, Auteur ; J. NGUYEN, Auteur ; J. BERG, Auteur ; M. STARKS, Auteur ; Daniel H. GESCHWIND, Auteur Article en page(s) : 25p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Cyfip1  Dup15q  Fear conditioning  Mouse behavior  Neurodevelopmental disorders  RNA sequencing Index. décimale : PER Périodiques Résumé : Background: CYFIP1, a protein that interacts with FMRP and regulates protein synthesis and actin dynamics, is overexpressed in Dup15q syndrome as well as autism spectrum disorder (ASD). While CYFIP1 heterozygosity has been rigorously studied due to its loss in 15q11.2 deletion, Prader-Willi and Angelman syndrome, the effects of CYFIP1 overexpression, as is observed in patients with CYFIP1 duplication, are less well understood. Methods: We developed and validated a mouse model of human CYFIP1 overexpression (CYFIP1 OE) using qPCR and western blot analysis. We performed a large battery of behavior testing on these mice, including ultrasonic vocalizations, three-chamber social assay, home-cage behavior, Y-maze, elevated plus maze, open field test, Morris water maze, fear conditioning, prepulse inhibition, and the hot plate assay. We also performed RNA sequencing and analysis on the basolateral amygdala. Results: Extensive behavioral testing in CYFIP1 OE mice reveals no changes in the core behaviors related to ASD: social interactions and repetitive behaviors. However, we did observe mild learning deficits and an exaggerated fear response. Using RNA sequencing of the basolateral amygdala, a region associated with fear response, we observed changes in pathways related to cytoskeletal regulation, oligodendrocytes, and myelination. We also identified GABA-A subunit composition changes in basolateral amygdala neurons, which are essential components of the neural fear conditioning circuit. Conclusion: Overall, this research identifies the behavioral and molecular consequences of CYFIP1 overexpression and how they contribute to the variable phenotype seen in Dup15q syndrome and in ASD patients with excess CYFIP1. En ligne : http://dx.doi.org/10.1186/s13229-019-0278-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 [article] CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes [Texte imprimé et/ou numérique] / C. FRICANO-KUGLER, Auteur ; A. GORDON, Auteur ; G. SHIN, Auteur ; K. GAO, Auteur ; J. NGUYEN, Auteur ; J. BERG, Auteur ; M. STARKS, Auteur ; Daniel H. GESCHWIND, Auteur . - 25p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 25p. Mots-clés : Autism spectrum disorder (ASD)  Cyfip1  Dup15q  Fear conditioning  Mouse behavior  Neurodevelopmental disorders  RNA sequencing Index. décimale : PER Périodiques Résumé : Background: CYFIP1, a protein that interacts with FMRP and regulates protein synthesis and actin dynamics, is overexpressed in Dup15q syndrome as well as autism spectrum disorder (ASD). While CYFIP1 heterozygosity has been rigorously studied due to its loss in 15q11.2 deletion, Prader-Willi and Angelman syndrome, the effects of CYFIP1 overexpression, as is observed in patients with CYFIP1 duplication, are less well understood. Methods: We developed and validated a mouse model of human CYFIP1 overexpression (CYFIP1 OE) using qPCR and western blot analysis. We performed a large battery of behavior testing on these mice, including ultrasonic vocalizations, three-chamber social assay, home-cage behavior, Y-maze, elevated plus maze, open field test, Morris water maze, fear conditioning, prepulse inhibition, and the hot plate assay. We also performed RNA sequencing and analysis on the basolateral amygdala. Results: Extensive behavioral testing in CYFIP1 OE mice reveals no changes in the core behaviors related to ASD: social interactions and repetitive behaviors. However, we did observe mild learning deficits and an exaggerated fear response. Using RNA sequencing of the basolateral amygdala, a region associated with fear response, we observed changes in pathways related to cytoskeletal regulation, oligodendrocytes, and myelination. We also identified GABA-A subunit composition changes in basolateral amygdala neurons, which are essential components of the neural fear conditioning circuit. Conclusion: Overall, this research identifies the behavioral and molecular consequences of CYFIP1 overexpression and how they contribute to the variable phenotype seen in Dup15q syndrome and in ASD patients with excess CYFIP1. En ligne : http://dx.doi.org/10.1186/s13229-019-0278-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402

The distribution of autistic traits across the autism spectrum: evidence for discontinuous dimensional subpopulations underlying the autism continuum / Ahmad ABU-AKEL in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 24p. Titre : The distribution of autistic traits across the autism spectrum: evidence for discontinuous dimensional subpopulations underlying the autism continuum Type de document : Texte imprimé et/ou numérique Auteurs : Ahmad ABU-AKEL, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur ; D. HEINKE, Auteur Article en page(s) : 24p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background: A considerable amount of research has discussed whether autism and psychiatric/neurodevelopmental conditions in general are best described categorically or dimensionally. In recent years, finite mixture models have been increasingly applied to mixed populations of autistic and non-autistic individuals to answer this question. However, the use of such methods with mixed populations may not be appropriate for two reasons: First, subgroups within mixed populations are often skewed and thus violate mixture models assumptions, which are based on weighted sum of Gaussian distributions. Second, these analyses have, to our knowledge, been solely applied to enriched samples, where the prevalence of the clinical condition within the study sample far exceeds epidemiological estimates. Method: We employed a dual Weibull mixture model to examine the distribution of the Autism Spectrum Quotient scores of a mixed sample of autistic and non-autistic adults (N = 4717; autism = 811), as well as of a derived sample (from the enriched sample; N = 3973; autism = 67) that reflects the current prevalence of autism within the general population. Results: In a mixed autistic and non-autistic population, our model provided a better description of the underlying structure of autistic traits than traditional finite Gaussian mixture models and performed well when applied to a sample that reflected the prevalence of autism in the general population. The model yielded results, which are consistent with predictions of current theories advocating for the co-existence of a mixed categorical and dimensional architecture within the autism spectrum. Conclusion: The results provide insight into the continuum nature of the distribution of autistic traits, support the complementary role of both categorical and dimensional approaches to autism spectrum condition, and underscore the importance of analyzing samples that reflect the epidemiological prevalence of the condition. Owing to its flexibility to represent a wide variety of distributions, the Weibull distribution might be better suited for latent structure studies, within enriched and prevalence-true samples. En ligne : http://dx.doi.org/10.1186/s13229-019-0275-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 [article] The distribution of autistic traits across the autism spectrum: evidence for discontinuous dimensional subpopulations underlying the autism continuum [Texte imprimé et/ou numérique] / Ahmad ABU-AKEL, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur ; D. HEINKE, Auteur . - 24p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 24p. Index. décimale : PER Périodiques Résumé : Background: A considerable amount of research has discussed whether autism and psychiatric/neurodevelopmental conditions in general are best described categorically or dimensionally. In recent years, finite mixture models have been increasingly applied to mixed populations of autistic and non-autistic individuals to answer this question. However, the use of such methods with mixed populations may not be appropriate for two reasons: First, subgroups within mixed populations are often skewed and thus violate mixture models assumptions, which are based on weighted sum of Gaussian distributions. Second, these analyses have, to our knowledge, been solely applied to enriched samples, where the prevalence of the clinical condition within the study sample far exceeds epidemiological estimates. Method: We employed a dual Weibull mixture model to examine the distribution of the Autism Spectrum Quotient scores of a mixed sample of autistic and non-autistic adults (N = 4717; autism = 811), as well as of a derived sample (from the enriched sample; N = 3973; autism = 67) that reflects the current prevalence of autism within the general population. Results: In a mixed autistic and non-autistic population, our model provided a better description of the underlying structure of autistic traits than traditional finite Gaussian mixture models and performed well when applied to a sample that reflected the prevalence of autism in the general population. The model yielded results, which are consistent with predictions of current theories advocating for the co-existence of a mixed categorical and dimensional architecture within the autism spectrum. Conclusion: The results provide insight into the continuum nature of the distribution of autistic traits, support the complementary role of both categorical and dimensional approaches to autism spectrum condition, and underscore the importance of analyzing samples that reflect the epidemiological prevalence of the condition. Owing to its flexibility to represent a wide variety of distributions, the Weibull distribution might be better suited for latent structure studies, within enriched and prevalence-true samples. En ligne : http://dx.doi.org/10.1186/s13229-019-0275-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402

Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes / M. SONZOGNI in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 23p. Titre : Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : M. SONZOGNI, Auteur ; J. HAKONEN, Auteur ; M. BERNABE KLEIJN, Auteur ; S. SILVA-SANTOS, Auteur ; M. C. JUDSON, Auteur ; B. D. PHILPOT, Auteur ; G. M. VAN WOERDEN, Auteur ; Y. ELGERSMA, Auteur Article en page(s) : 23p. Langues : Anglais (eng) Mots-clés : Angelman syndrome  Autism spectrum disorder  Mouse model  Phenotype  Seizure  Ube3a Index. décimale : PER Périodiques Résumé : Background: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutations affecting UBE3A gene expression. Previous studies in mice revealed distinct critical periods during neurodevelopment in which reactivation of Ube3a gene expression can prevent the onset of behavioral deficits. Whether UBE3A is required for brain function throughout life is unknown. Here, we address the importance of maintaining UBE3A expression after normal brain development. Findings: Using a conditional mouse, we deleted the Ube3a gene at three ages spanning brain maturation. We assessed the consequences of Ube3a gene deletion by testing the mice in behavioral tasks previously shown to produce robust phenotypes in AS model mice. Early embryonic deletion of Ube3a recapitulated all behavioral deficits of AS mice. In contrast, Ube3a gene deletion at 3 or 12 weeks of age did not have a significant effect on most behavioral tasks and did not increase seizure sensitivity. Conclusions: Taken together, these results emphasize that UBE3A critically impacts early brain development, but plays a more limited role in adulthood. Our findings provide important considerations for upcoming clinical trials in which UBE3A gene expression is reactivated and suggest that even transient UBE3A reinstatement during a critical window of early development is likely to prevent most adverse Angelman syndrome phenotypes. However, sustained UBE3A expression into adulthood is probably needed for optimal clinical benefit. En ligne : http://dx.doi.org/10.1186/s13229-019-0277-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 [article] Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes [Texte imprimé et/ou numérique] / M. SONZOGNI, Auteur ; J. HAKONEN, Auteur ; M. BERNABE KLEIJN, Auteur ; S. SILVA-SANTOS, Auteur ; M. C. JUDSON, Auteur ; B. D. PHILPOT, Auteur ; G. M. VAN WOERDEN, Auteur ; Y. ELGERSMA, Auteur . - 23p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 23p. Mots-clés : Angelman syndrome  Autism spectrum disorder  Mouse model  Phenotype  Seizure  Ube3a Index. décimale : PER Périodiques Résumé : Background: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutations affecting UBE3A gene expression. Previous studies in mice revealed distinct critical periods during neurodevelopment in which reactivation of Ube3a gene expression can prevent the onset of behavioral deficits. Whether UBE3A is required for brain function throughout life is unknown. Here, we address the importance of maintaining UBE3A expression after normal brain development. Findings: Using a conditional mouse, we deleted the Ube3a gene at three ages spanning brain maturation. We assessed the consequences of Ube3a gene deletion by testing the mice in behavioral tasks previously shown to produce robust phenotypes in AS model mice. Early embryonic deletion of Ube3a recapitulated all behavioral deficits of AS mice. In contrast, Ube3a gene deletion at 3 or 12 weeks of age did not have a significant effect on most behavioral tasks and did not increase seizure sensitivity. Conclusions: Taken together, these results emphasize that UBE3A critically impacts early brain development, but plays a more limited role in adulthood. Our findings provide important considerations for upcoming clinical trials in which UBE3A gene expression is reactivated and suggest that even transient UBE3A reinstatement during a critical window of early development is likely to prevent most adverse Angelman syndrome phenotypes. However, sustained UBE3A expression into adulthood is probably needed for optimal clinical benefit. En ligne : http://dx.doi.org/10.1186/s13229-019-0277-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402

Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events? / M. BENNABI in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 22p. Titre : Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events? Type de document : Texte imprimé et/ou numérique Auteurs : M. BENNABI, Auteur ; N. TARANTINO, Auteur ; A. GAMAN, Auteur ; Isabelle SCHEID, Auteur ; R. KRISHNAMOORTHY, Auteur ; P. DEBRE, Auteur ; A. BOULEAU, Auteur ; M. CARALP, Auteur ; S. GUEGUEN, Auteur ; M. L. LE-MOAL, Auteur ; Manuel P. BOUVARD, Auteur ; Anouck AMESTOY, Auteur ; R. DELORME, Auteur ; M. LEBOYER, Auteur ; R. TAMOUZA, Auteur ; V. VIEILLARD, Auteur Article en page(s) : 22p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  High-functioning autism  Natural killer cells  Pathogens Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) are characterized by abnormal neurodevelopment, genetic, and environmental risk factors, as well as immune dysfunctions. Several lines of evidence suggest alterations in innate immune responses in children with ASD. To address this question in adults with high-functioning ASD (hf-ASD), we sought to investigate the role of natural killer (NK) cells in the persistence of ASD. Methods: NK cells from 35 adults with hf-ASD were compared to that of 35 healthy controls (HC), selected for the absence of any immune dysfunctions, at different time-points, and over a 2-year follow-up period for four patients. The phenotype and polyfunctional capacities of NK cells were explored according to infectious stigma and clinical parameters (IQ, social, and communication scores). Results: As compared to HC, NK cells from patients with hf-ASD showed a high level of cell activation (p < 0.0001), spontaneous degranulation (p < 0.0001), and interferon-gamma production (p = 0.0004), whereas they were exhausted after in vitro stimulations (p = 0.0006). These data yielded a specific HLA-DR(+)KIR2DL1(+)NKG2C(+) NK-cell signature. Significant overexpression of NKG2C in hf-ASD patients (p = 0.0005), indicative of viral infections, was inversely correlated with the NKp46 receptor level (r = - 0.67; p < 0.0001), regardless of the IgG status of tested pathogens. Multivariate linear regression analysis also revealed that expression of the late-activating HLA-DR marker was both associated with structural language (r = 0.48; p = 0.007) and social awareness (r = 0.60; p = 0.0007) scores in adult patients with hf-ASD, while KIR2DL1 expression correlated with IQ scores (p = 0.0083). Conclusions: This study demonstrates that adults with hf-ASD have specific NK-cell profile. Presence of NKG2C overexpression together with high-level activation of NK cells suggest an association with underlying pathogens, a hypothesis warranting further exploration in future studies. En ligne : http://dx.doi.org/10.1186/s13229-019-0269-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 [article] Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events? [Texte imprimé et/ou numérique] / M. BENNABI, Auteur ; N. TARANTINO, Auteur ; A. GAMAN, Auteur ; Isabelle SCHEID, Auteur ; R. KRISHNAMOORTHY, Auteur ; P. DEBRE, Auteur ; A. BOULEAU, Auteur ; M. CARALP, Auteur ; S. GUEGUEN, Auteur ; M. L. LE-MOAL, Auteur ; Manuel P. BOUVARD, Auteur ; Anouck AMESTOY, Auteur ; R. DELORME, Auteur ; M. LEBOYER, Auteur ; R. TAMOUZA, Auteur ; V. VIEILLARD, Auteur . - 22p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 22p. Mots-clés : Autism spectrum disorders  High-functioning autism  Natural killer cells  Pathogens Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) are characterized by abnormal neurodevelopment, genetic, and environmental risk factors, as well as immune dysfunctions. Several lines of evidence suggest alterations in innate immune responses in children with ASD. To address this question in adults with high-functioning ASD (hf-ASD), we sought to investigate the role of natural killer (NK) cells in the persistence of ASD. Methods: NK cells from 35 adults with hf-ASD were compared to that of 35 healthy controls (HC), selected for the absence of any immune dysfunctions, at different time-points, and over a 2-year follow-up period for four patients. The phenotype and polyfunctional capacities of NK cells were explored according to infectious stigma and clinical parameters (IQ, social, and communication scores). Results: As compared to HC, NK cells from patients with hf-ASD showed a high level of cell activation (p < 0.0001), spontaneous degranulation (p < 0.0001), and interferon-gamma production (p = 0.0004), whereas they were exhausted after in vitro stimulations (p = 0.0006). These data yielded a specific HLA-DR(+)KIR2DL1(+)NKG2C(+) NK-cell signature. Significant overexpression of NKG2C in hf-ASD patients (p = 0.0005), indicative of viral infections, was inversely correlated with the NKp46 receptor level (r = - 0.67; p < 0.0001), regardless of the IgG status of tested pathogens. Multivariate linear regression analysis also revealed that expression of the late-activating HLA-DR marker was both associated with structural language (r = 0.48; p = 0.007) and social awareness (r = 0.60; p = 0.0007) scores in adult patients with hf-ASD, while KIR2DL1 expression correlated with IQ scores (p = 0.0083). Conclusions: This study demonstrates that adults with hf-ASD have specific NK-cell profile. Presence of NKG2C overexpression together with high-level activation of NK cells suggest an association with underlying pathogens, a hypothesis warranting further exploration in future studies. En ligne : http://dx.doi.org/10.1186/s13229-019-0269-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402

Generalizability and reproducibility of functional connectivity in autism / J. B. KING in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 27 p. Titre : Generalizability and reproducibility of functional connectivity in autism Type de document : Texte imprimé et/ou numérique Auteurs : J. B. KING, Auteur ; M. B. D. PRIGGE, Auteur ; C. K. KING, Auteur ; J. MORGAN, Auteur ; F. WEATHERSBY, Auteur ; J. C. FOX, Auteur ; D. C. DEAN, Auteur ; A. FREEMAN, Auteur ; J. A. M. VILLARUZ, Auteur ; Karen L. KANE, Auteur ; Erin D. BIGLER, Auteur ; A. L. ALEXANDER, Auteur ; N. LANGE, Auteur ; B. ZIELINSKI, Auteur ; J. E. LAINHART, Auteur ; Jeffrey S. ANDERSON, Auteur Article en page(s) : 27 p. Langues : Anglais (eng) Mots-clés : Autism spectrum conditions  Functional connectivity MRI  Replicability  Reproducibility  Resting-state  fMRI Index. décimale : PER Périodiques Résumé : Background: Autism is hypothesized to represent a disorder of brain connectivity, yet patterns of atypical functional connectivity show marked heterogeneity across individuals. Methods: We used a large multi-site dataset comprised of a heterogeneous population of individuals with autism and typically developing individuals to compare a number of resting-state functional connectivity features of autism. These features were also tested in a single site sample that utilized a high-temporal resolution, long-duration resting-state acquisition technique. Results: No one method of analysis provided reproducible results across research sites, combined samples, and the high-resolution dataset. Distinct categories of functional connectivity features that differed in autism such as homotopic, default network, salience network, long-range connections, and corticostriatal connectivity, did not align with differences in clinical and behavioral traits in individuals with autism. One method, lag-based functional connectivity, was not correlated to other methods in describing patterns of resting-state functional connectivity and their relationship to autism traits. Conclusion: Overall, functional connectivity features predictive of autism demonstrated limited generalizability across sites, with consistent results only for large samples. Different types of functional connectivity features do not consistently predict different symptoms of autism. Rather, specific features that predict autism symptoms are distributed across feature types. En ligne : https://dx.doi.org/10.1186/s13229-019-0273-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Generalizability and reproducibility of functional connectivity in autism [Texte imprimé et/ou numérique] / J. B. KING, Auteur ; M. B. D. PRIGGE, Auteur ; C. K. KING, Auteur ; J. MORGAN, Auteur ; F. WEATHERSBY, Auteur ; J. C. FOX, Auteur ; D. C. DEAN, Auteur ; A. FREEMAN, Auteur ; J. A. M. VILLARUZ, Auteur ; Karen L. KANE, Auteur ; Erin D. BIGLER, Auteur ; A. L. ALEXANDER, Auteur ; N. LANGE, Auteur ; B. ZIELINSKI, Auteur ; J. E. LAINHART, Auteur ; Jeffrey S. ANDERSON, Auteur . - 27 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 27 p. Mots-clés : Autism spectrum conditions  Functional connectivity MRI  Replicability  Reproducibility  Resting-state  fMRI Index. décimale : PER Périodiques Résumé : Background: Autism is hypothesized to represent a disorder of brain connectivity, yet patterns of atypical functional connectivity show marked heterogeneity across individuals. Methods: We used a large multi-site dataset comprised of a heterogeneous population of individuals with autism and typically developing individuals to compare a number of resting-state functional connectivity features of autism. These features were also tested in a single site sample that utilized a high-temporal resolution, long-duration resting-state acquisition technique. Results: No one method of analysis provided reproducible results across research sites, combined samples, and the high-resolution dataset. Distinct categories of functional connectivity features that differed in autism such as homotopic, default network, salience network, long-range connections, and corticostriatal connectivity, did not align with differences in clinical and behavioral traits in individuals with autism. One method, lag-based functional connectivity, was not correlated to other methods in describing patterns of resting-state functional connectivity and their relationship to autism traits. Conclusion: Overall, functional connectivity features predictive of autism demonstrated limited generalizability across sites, with consistent results only for large samples. Different types of functional connectivity features do not consistently predict different symptoms of autism. Rather, specific features that predict autism symptoms are distributed across feature types. En ligne : https://dx.doi.org/10.1186/s13229-019-0273-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Visual attention to faces in children with autism spectrum disorder: are there sex differences? / C. HARROP in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 28 p. Titre : Visual attention to faces in children with autism spectrum disorder: are there sex differences? Type de document : Texte imprimé et/ou numérique Auteurs : C. HARROP, Auteur ; D. JONES, Auteur ; S. ZHENG, Auteur ; Sallie W. NOWELL, Auteur ; R. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur Article en page(s) : 28 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Eye gaze  Sex differences  Social attention  Social cognition Index. décimale : PER Périodiques Résumé : Background: The male bias in autism spectrum disorder (ASD) diagnoses is well documented. As a result, less is known about the female ASD phenotype. Recent research suggests that conclusions drawn from predominantly male samples may not accurately capture female behavior. In this study, we explore potential sex differences in attention to social stimuli, which is generally reported to be diminished in ASD. Population-based sex differences in attention to faces have been reported, such that typically developing (TD) females attend more to social stimuli (including faces) from infancy through adulthood than TD males. It is yet unknown whether population-based sex differences in the face domain are preserved in ASD. Methods: A dynamic, naturalistic infrared eye-tracking paradigm measured attention to social stimuli (faces) in 74 school-aged males and females with ASD (male N = 23; female N = 19) and without ASD (male N = 16; female N = 16). Two kinds of video stimuli were presented that varied in social content: rich social scenes (dyadic play between two children) and lean social scenes (parallel play by two children). Results: Results revealed a significant 3-way interaction between sex, diagnosis, and condition after controlling for chronological and mental age. ASD females attended more to faces than ASD males in the socially lean condition. This effect was not found in the typically developing (TD) group. ASD males attended less to faces regardless of social context; however, ASD females only attended significantly less to faces compared to TD females in the socially rich condition. TD males and ASD females did not differ in their attention to faces in either condition. Conclusions: This study has implications for how the field understands core social deficits in children with ASD, which should ideally be benchmarked against same-sex peers (male and female). Social attention in ASD females fell on a continuum-greater than their ASD male peers, but not as great as TD females. Overall, their social attention mirrored that of TD males. Improved understanding of the female social phenotype in ASD will enhance early screening and diagnostic efforts and will guide the development of sex-sensitive experimental paradigms and social interventions. En ligne : https://dx.doi.org/10.1186/s13229-019-0276-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Visual attention to faces in children with autism spectrum disorder: are there sex differences? [Texte imprimé et/ou numérique] / C. HARROP, Auteur ; D. JONES, Auteur ; S. ZHENG, Auteur ; Sallie W. NOWELL, Auteur ; R. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur . - 28 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 28 p. Mots-clés : Autism spectrum disorder  Eye gaze  Sex differences  Social attention  Social cognition Index. décimale : PER Périodiques Résumé : Background: The male bias in autism spectrum disorder (ASD) diagnoses is well documented. As a result, less is known about the female ASD phenotype. Recent research suggests that conclusions drawn from predominantly male samples may not accurately capture female behavior. In this study, we explore potential sex differences in attention to social stimuli, which is generally reported to be diminished in ASD. Population-based sex differences in attention to faces have been reported, such that typically developing (TD) females attend more to social stimuli (including faces) from infancy through adulthood than TD males. It is yet unknown whether population-based sex differences in the face domain are preserved in ASD. Methods: A dynamic, naturalistic infrared eye-tracking paradigm measured attention to social stimuli (faces) in 74 school-aged males and females with ASD (male N = 23; female N = 19) and without ASD (male N = 16; female N = 16). Two kinds of video stimuli were presented that varied in social content: rich social scenes (dyadic play between two children) and lean social scenes (parallel play by two children). Results: Results revealed a significant 3-way interaction between sex, diagnosis, and condition after controlling for chronological and mental age. ASD females attended more to faces than ASD males in the socially lean condition. This effect was not found in the typically developing (TD) group. ASD males attended less to faces regardless of social context; however, ASD females only attended significantly less to faces compared to TD females in the socially rich condition. TD males and ASD females did not differ in their attention to faces in either condition. Conclusions: This study has implications for how the field understands core social deficits in children with ASD, which should ideally be benchmarked against same-sex peers (male and female). Social attention in ASD females fell on a continuum-greater than their ASD male peers, but not as great as TD females. Overall, their social attention mirrored that of TD males. Improved understanding of the female social phenotype in ASD will enhance early screening and diagnostic efforts and will guide the development of sex-sensitive experimental paradigms and social interventions. En ligne : https://dx.doi.org/10.1186/s13229-019-0276-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Mechanisms underlying the EEG biomarker in Dup15q syndrome / J. FROHLICH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 29 p. Titre : Mechanisms underlying the EEG biomarker in Dup15q syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. FROHLICH, Auteur ; L. T. REITER, Auteur ; V. SARAVANAPANDIAN, Auteur ; C. DISTEFANO, Auteur ; S. HUBERTY, Auteur ; C. HYDE, Auteur ; S. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; P. GOLSHANI, Auteur ; A. IRIMIA, Auteur ; R. W. OLSEN, Auteur ; J. F. HIPP, Auteur ; S. S. JESTE, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gaba  Gabra5  Gabrb3  Gabrg3  Neurodevelopmental disorders  UBE3A Index. décimale : PER Périodiques Résumé : Background: Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods: To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results: Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions: Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome. En ligne : https://dx.doi.org/10.1186/s13229-019-0280-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Mechanisms underlying the EEG biomarker in Dup15q syndrome [Texte imprimé et/ou numérique] / J. FROHLICH, Auteur ; L. T. REITER, Auteur ; V. SARAVANAPANDIAN, Auteur ; C. DISTEFANO, Auteur ; S. HUBERTY, Auteur ; C. HYDE, Auteur ; S. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; P. GOLSHANI, Auteur ; A. IRIMIA, Auteur ; R. W. OLSEN, Auteur ; J. F. HIPP, Auteur ; S. S. JESTE, Auteur . - 29 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 29 p. Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gaba  Gabra5  Gabrb3  Gabrg3  Neurodevelopmental disorders  UBE3A Index. décimale : PER Périodiques Résumé : Background: Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods: To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results: Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions: Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome. En ligne : https://dx.doi.org/10.1186/s13229-019-0280-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits / A. MASSRALI in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 31 p. Titre : Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits Type de document : Texte imprimé et/ou numérique Auteurs : A. MASSRALI, Auteur ; H. BRUNEL, Auteur ; E. HANNON, Auteur ; C. WONG, Auteur ; Simon BARON-COHEN, Auteur ; V. WARRIER, Auteur Article en page(s) : 31 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Previous studies have identified differences in DNA methylation in autistic individuals compared to neurotypical individuals. Yet, it is unclear if this extends to autistic traits-subclinical manifestation of autism features in the general population. Here, we investigate the association between DNA methylation at birth (cord blood), and scores on the Social and Communication Disorders Checklist (SCDC), a measure of autistic traits, in 701 8-year-olds, by conducting a methylome-wide association study (MWAS). We did not identify significant CpGs associated with SCDC. The most significant CpG site was cg14379490, on chromosome 9 (MWAS beta = - 1.78 +/- 0.35, p value = 5.34 x 10 (-7) ). Using methylation data for autism in peripheral tissues, we did not identify a significant concordance in effect direction of CpGs with p value < 10(-4) in the SCDC MWAS (binomial sign test, p value > 0.5). In contrast, using methylation data for autism from post-mortem brain tissues, we identify a significant concordance in effect direction of CpGs with a p value < 10(-4) in the SCDC MWAS (binomial sign test, p value = 0.004). Supporting this, we observe an enrichment for genes that are dysregulated in the post-mortem autism brain (one-sided Wilcoxon rank-sum test, p value = 6.22 x 10(-5)). Finally, integrating genome-wide association study (GWAS) data for autism (n = 46,350) with mQTL maps from cord-blood (n = 771), we demonstrate that mQTLs of CpGs associated with SCDC scores at p value thresholds of 0.01 and 0.005 are significantly shifted toward lower p values in the GWAS for autism (p < 5 x 10(-3)). We provide additional support for this using a GWAS of SCDC, and demonstrate a lack of enrichment in a GWAS of Alzheimer's disease. Our results highlight the shared cross-tissue methylation architecture of autism and autistic traits, and demonstrate that mQTLs associated with differences in DNA methylation associated with childhood autistic traits are enriched for common genetic variants associated with autism and autistic traits. En ligne : https://dx.doi.org/10.1186/s13229-019-0279-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits [Texte imprimé et/ou numérique] / A. MASSRALI, Auteur ; H. BRUNEL, Auteur ; E. HANNON, Auteur ; C. WONG, Auteur ; Simon BARON-COHEN, Auteur ; V. WARRIER, Auteur . - 31 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 31 p. Index. décimale : PER Périodiques Résumé : Previous studies have identified differences in DNA methylation in autistic individuals compared to neurotypical individuals. Yet, it is unclear if this extends to autistic traits-subclinical manifestation of autism features in the general population. Here, we investigate the association between DNA methylation at birth (cord blood), and scores on the Social and Communication Disorders Checklist (SCDC), a measure of autistic traits, in 701 8-year-olds, by conducting a methylome-wide association study (MWAS). We did not identify significant CpGs associated with SCDC. The most significant CpG site was cg14379490, on chromosome 9 (MWAS beta = - 1.78 +/- 0.35, p value = 5.34 x 10 (-7) ). Using methylation data for autism in peripheral tissues, we did not identify a significant concordance in effect direction of CpGs with p value < 10(-4) in the SCDC MWAS (binomial sign test, p value > 0.5). In contrast, using methylation data for autism from post-mortem brain tissues, we identify a significant concordance in effect direction of CpGs with a p value < 10(-4) in the SCDC MWAS (binomial sign test, p value = 0.004). Supporting this, we observe an enrichment for genes that are dysregulated in the post-mortem autism brain (one-sided Wilcoxon rank-sum test, p value = 6.22 x 10(-5)). Finally, integrating genome-wide association study (GWAS) data for autism (n = 46,350) with mQTL maps from cord-blood (n = 771), we demonstrate that mQTLs of CpGs associated with SCDC scores at p value thresholds of 0.01 and 0.005 are significantly shifted toward lower p values in the GWAS for autism (p < 5 x 10(-3)). We provide additional support for this using a GWAS of SCDC, and demonstrate a lack of enrichment in a GWAS of Alzheimer's disease. Our results highlight the shared cross-tissue methylation architecture of autism and autistic traits, and demonstrate that mQTLs associated with differences in DNA methylation associated with childhood autistic traits are enriched for common genetic variants associated with autism and autistic traits. En ligne : https://dx.doi.org/10.1186/s13229-019-0279-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Neuropsychiatric phenotypes and a distinct constellation of ASD features in 3q29 deletion syndrome: results from the 3q29 registry / R. M. POLLAK in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 30 p. Titre : Neuropsychiatric phenotypes and a distinct constellation of ASD features in 3q29 deletion syndrome: results from the 3q29 registry Type de document : Texte imprimé et/ou numérique Auteurs : R. M. POLLAK, Auteur ; M. M. MURPHY, Auteur ; M. P. EPSTEIN, Auteur ; M. E. ZWICK, Auteur ; C. KLAIMAN, Auteur ; Celine A. SAULNIER, Auteur ; J. G. MULLE, Auteur Article en page(s) : 30 p. Langues : Anglais (eng) Mots-clés : 3q29 deletion  Autism  Copy number variants  Developmental delay  Genomic disorder  Psychiatric genetics  SRS  Vineland-3 Index. décimale : PER Périodiques Résumé : Background: The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20 to 40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described. Methods: We ascertained individuals with 3q29 deletion syndrome (3q29Del, "cases," n = 93, 58.1% male) and typically developing controls (n = 64, 51.6% male) through the 3q29 registry (https://3q29deletion.patientcrossroads.org). Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n = 48 cases, 56 controls), Social Communication Questionnaire (n = 33 cases, 46 controls), Autism Spectrum Screening Questionnaire (n = 24 cases, 35 controls), and Achenbach Behavior Checklists (n = 48 cases, 57 controls). Results: 3q29Del cases report a higher prevalence of autism diagnoses versus the general population (29.0% vs. 1.47%, p < 2.2E- 16). Notably, 3q29 deletion confers a greater influence on risk for ASD in females (OR = 41.8, p = 4.78E- 05) than in males (OR = 24.6, p = 6.06E- 09); this is aligned with the reduced male:female bias from 4:1 in the general population to 2:1 in our study sample. Although 71% of cases do not report a diagnosis of ASD, there is evidence of significant social disability (3q29Del SRS T-score = 71.8, control SRS T-score = 45.9, p = 2.16E- 13). Cases also report increased frequency of generalized anxiety disorder compared to controls (28.0% vs. 6.2%, p = 0.001), which is mirrored by elevated mean scores on the Achenbach diagnostic and statistical manual-oriented sub-scales (p < 0.001). Finally, cases show a distinct constellation of ASD features on the SRS as compared to idiopathic ASD, with substantially elevated Restricted Interests and Repetitive Behaviors, but only mild impairment in Social Motivation. Conclusions: Our sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the constellation of ASD features in this population is distinct from idiopathic ASD, with substantially less impaired social motivation. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the distinct ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0281-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Neuropsychiatric phenotypes and a distinct constellation of ASD features in 3q29 deletion syndrome: results from the 3q29 registry [Texte imprimé et/ou numérique] / R. M. POLLAK, Auteur ; M. M. MURPHY, Auteur ; M. P. EPSTEIN, Auteur ; M. E. ZWICK, Auteur ; C. KLAIMAN, Auteur ; Celine A. SAULNIER, Auteur ; J. G. MULLE, Auteur . - 30 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 30 p. Mots-clés : 3q29 deletion  Autism  Copy number variants  Developmental delay  Genomic disorder  Psychiatric genetics  SRS  Vineland-3 Index. décimale : PER Périodiques Résumé : Background: The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20 to 40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described. Methods: We ascertained individuals with 3q29 deletion syndrome (3q29Del, "cases," n = 93, 58.1% male) and typically developing controls (n = 64, 51.6% male) through the 3q29 registry (https://3q29deletion.patientcrossroads.org). Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n = 48 cases, 56 controls), Social Communication Questionnaire (n = 33 cases, 46 controls), Autism Spectrum Screening Questionnaire (n = 24 cases, 35 controls), and Achenbach Behavior Checklists (n = 48 cases, 57 controls). Results: 3q29Del cases report a higher prevalence of autism diagnoses versus the general population (29.0% vs. 1.47%, p < 2.2E- 16). Notably, 3q29 deletion confers a greater influence on risk for ASD in females (OR = 41.8, p = 4.78E- 05) than in males (OR = 24.6, p = 6.06E- 09); this is aligned with the reduced male:female bias from 4:1 in the general population to 2:1 in our study sample. Although 71% of cases do not report a diagnosis of ASD, there is evidence of significant social disability (3q29Del SRS T-score = 71.8, control SRS T-score = 45.9, p = 2.16E- 13). Cases also report increased frequency of generalized anxiety disorder compared to controls (28.0% vs. 6.2%, p = 0.001), which is mirrored by elevated mean scores on the Achenbach diagnostic and statistical manual-oriented sub-scales (p < 0.001). Finally, cases show a distinct constellation of ASD features on the SRS as compared to idiopathic ASD, with substantially elevated Restricted Interests and Repetitive Behaviors, but only mild impairment in Social Motivation. Conclusions: Our sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the constellation of ASD features in this population is distinct from idiopathic ASD, with substantially less impaired social motivation. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the distinct ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0281-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Behavioral characteristics of autism spectrum disorder in very preterm birth children / L. W. CHEN in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 32 p. Titre : Behavioral characteristics of autism spectrum disorder in very preterm birth children Type de document : Texte imprimé et/ou numérique Auteurs : L. W. CHEN, Auteur ; S. T. WANG, Auteur ; L. W. WANG, Auteur ; Y. C. KAO, Auteur ; C. L. CHU, Auteur ; C. C. WU, Auteur ; Y. T. HSIEH, Auteur ; Chung-Hsin CHIANG, Auteur ; C. C. HUANG, Auteur Article en page(s) : 32 p. Langues : Anglais (eng) Mots-clés : Autism Diagnostic Interview-Revised  Autism Diagnostic Observation Schedule  Autism spectrum disorder  Preterm  Very low birth weight Index. décimale : PER Périodiques Résumé : Background: Lower gestational age may increase autism spectrum disorder (ASD) vulnerability; however, the incidence of ASD diagnosis through a direct assessment on every very preterm birth child on the population base remains unclear. Moreover, the behavioral characteristics of preterm birth ASD are unknown. Methods: Every very preterm birth child (gestational age < 32 weeks; birth weight < 1500 g) who was discharged from neonatal intensive care units in Southern Taiwan and prospectively followed to 5 years of age was evaluated using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). The term birth (gestational age > 37 weeks) ASD children characterized by ADOS and ADI-R were group matched to the preterm birth ASD by age at examination for comparison. ADOS severity scores were calculated by the Mann-Whitney U test and ADI-R by multivariate analysis of variance and canonical discriminant analysis. Results: Two hundred forty-six (87%) of the 283 very preterm survivors were followed prospectively to 5 years of age. Nineteen (7.7%) of the 246 children fulfilled the diagnostic criteria of ASD. After excluding 1 patient with cerebral palsy and profound mental disability, 18 preterm ASD children were compared with 44 term birth ASD children. The two ASD groups were comparable for age at examination, gender, and intelligence quotient. The two groups showed comparable ADOS severity scores in social affect deficits, restricted repetitive behaviors, and total score, but had differences in qualitative abnormalities in reciprocal social interaction (Wilks lambda F value = 6.2, P < 0.001) of ADI-R. Compared to term birth ASD children, preterm birth ASD children exhibited worse nonverbal behaviors that regulate social interaction (OR 2.59, 95% CI 1.41-4.73, P = 0.002) but more favorable peer relationships (OR 0.58, 95% CI 0.38-0.90, P = 0.01) and socioemotional reciprocity (OR 0.55, 95% CI 0.33-0.92, P = 0.02). In contrast to the heterogeneous severity of social reciprocity in the term ASD group, the behavioral characteristics of the preterm ASD group showed a homogeneous reciprocal social interaction pattern. Conclusions: The 5-year incidence rate of ASD was high in very preterm birth children. Preterm birth ASD exhibited a specific behavioral phenotype of reciprocal social interaction. En ligne : https://dx.doi.org/10.1186/s13229-019-0282-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Behavioral characteristics of autism spectrum disorder in very preterm birth children [Texte imprimé et/ou numérique] / L. W. CHEN, Auteur ; S. T. WANG, Auteur ; L. W. WANG, Auteur ; Y. C. KAO, Auteur ; C. L. CHU, Auteur ; C. C. WU, Auteur ; Y. T. HSIEH, Auteur ; Chung-Hsin CHIANG, Auteur ; C. C. HUANG, Auteur . - 32 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 32 p. Mots-clés : Autism Diagnostic Interview-Revised  Autism Diagnostic Observation Schedule  Autism spectrum disorder  Preterm  Very low birth weight Index. décimale : PER Périodiques Résumé : Background: Lower gestational age may increase autism spectrum disorder (ASD) vulnerability; however, the incidence of ASD diagnosis through a direct assessment on every very preterm birth child on the population base remains unclear. Moreover, the behavioral characteristics of preterm birth ASD are unknown. Methods: Every very preterm birth child (gestational age < 32 weeks; birth weight < 1500 g) who was discharged from neonatal intensive care units in Southern Taiwan and prospectively followed to 5 years of age was evaluated using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). The term birth (gestational age > 37 weeks) ASD children characterized by ADOS and ADI-R were group matched to the preterm birth ASD by age at examination for comparison. ADOS severity scores were calculated by the Mann-Whitney U test and ADI-R by multivariate analysis of variance and canonical discriminant analysis. Results: Two hundred forty-six (87%) of the 283 very preterm survivors were followed prospectively to 5 years of age. Nineteen (7.7%) of the 246 children fulfilled the diagnostic criteria of ASD. After excluding 1 patient with cerebral palsy and profound mental disability, 18 preterm ASD children were compared with 44 term birth ASD children. The two ASD groups were comparable for age at examination, gender, and intelligence quotient. The two groups showed comparable ADOS severity scores in social affect deficits, restricted repetitive behaviors, and total score, but had differences in qualitative abnormalities in reciprocal social interaction (Wilks lambda F value = 6.2, P < 0.001) of ADI-R. Compared to term birth ASD children, preterm birth ASD children exhibited worse nonverbal behaviors that regulate social interaction (OR 2.59, 95% CI 1.41-4.73, P = 0.002) but more favorable peer relationships (OR 0.58, 95% CI 0.38-0.90, P = 0.01) and socioemotional reciprocity (OR 0.55, 95% CI 0.33-0.92, P = 0.02). In contrast to the heterogeneous severity of social reciprocity in the term ASD group, the behavioral characteristics of the preterm ASD group showed a homogeneous reciprocal social interaction pattern. Conclusions: The 5-year incidence rate of ASD was high in very preterm birth children. Preterm birth ASD exhibited a specific behavioral phenotype of reciprocal social interaction. En ligne : https://dx.doi.org/10.1186/s13229-019-0282-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder / A. MUNNICH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 33 p. Titre : Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : A. MUNNICH, Auteur ; Caroline DEMILY, Auteur ; L. FRUGERE, Auteur ; C. DUWIME, Auteur ; V. MALAN, Auteur ; Giulia BARCIA, Auteur ; C. VIDAL, Auteur ; E. THROO, Auteur ; C. BESMOND, Auteur ; L. HUBERT, Auteur ; G. ROLAND-MANUEL, Auteur ; J. P. MALEN, Auteur ; M. FERRERI, Auteur ; S. HANEIN, Auteur ; J. C. THALABARD, Auteur ; Nathalie BODDAERT, Auteur ; Moïse ASSOULINE, Auteur Article en page(s) : 33 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Copy number variant  Fragile X syndrome  Gene panel  Genetic counseling  Genetic diagnosis  Microarray  Next-generation sequencing  Sequence variant Index. décimale : PER Périodiques Résumé : Background: Neurogenetics investigations and diagnostic yield in patients with autism spectrum disorder (ASD) have significantly improved over the last few years. Yet, many patients still fail to be systematically investigated. Methods: To improve access to services, an ambulatory team has been established since 1998, delivering on-site clinical genetics consultations and gradually upgrading services to 502 children and young adults with ASD in their standard environment across 26 day-care hospitals and specialized institutions within the Greater Paris region. The evaluation included a clinical genetics consultation, screening for fragile X syndrome, metabolic workup, chromosomal microarray analysis, and, in a proportion of patients, next-generation sequencing of genes reported in ASD and other neurodevelopmental disorders. Results: Fragile X syndrome and pathogenic copy number variants (CNVs) accounted for the disease in 10% of cases, including 4/312 (1.3%) with fragile X syndrome and 34/388 (8.8%) with pathogenic CNVs (19 de novo and 4 inherited). Importantly, adding high-throughput resequencing of reported intellectual disability/ASD genes to the screening procedure had a major impact on diagnostic yield in the 141 patients examined most recently. Pathogenic or likely pathogenic sequence variants in 27 disease genes were identified in 33/141 patients (23.4%; 23 were de novo and 10 inherited, including five X-linked and five recessive compound heterozygous variants). Diagnosed cases presented atypical and/or syndromic ASD with moderate to severe intellectual disability. The diagnostic yield of fragile X syndrome and array CGH testing combined with next-generation sequencing was significantly higher than fragile X syndrome and array CGH alone (p value 0.009). No inborn errors of metabolism were detected with the metabolic screening. Conclusion: Based on the diagnostic rate observed in this cohort, we suggest that a stepwise procedure be considered, first screening pathogenic CNVs and a limited number of disease genes in a much larger number of patients, especially those with syndromic ASD and intellectual disability. En ligne : https://dx.doi.org/10.1186/s13229-019-0284-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder [Texte imprimé et/ou numérique] / A. MUNNICH, Auteur ; Caroline DEMILY, Auteur ; L. FRUGERE, Auteur ; C. DUWIME, Auteur ; V. MALAN, Auteur ; Giulia BARCIA, Auteur ; C. VIDAL, Auteur ; E. THROO, Auteur ; C. BESMOND, Auteur ; L. HUBERT, Auteur ; G. ROLAND-MANUEL, Auteur ; J. P. MALEN, Auteur ; M. FERRERI, Auteur ; S. HANEIN, Auteur ; J. C. THALABARD, Auteur ; Nathalie BODDAERT, Auteur ; Moïse ASSOULINE, Auteur . - 33 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 33 p. Mots-clés : Autism spectrum disorder  Copy number variant  Fragile X syndrome  Gene panel  Genetic counseling  Genetic diagnosis  Microarray  Next-generation sequencing  Sequence variant Index. décimale : PER Périodiques Résumé : Background: Neurogenetics investigations and diagnostic yield in patients with autism spectrum disorder (ASD) have significantly improved over the last few years. Yet, many patients still fail to be systematically investigated. Methods: To improve access to services, an ambulatory team has been established since 1998, delivering on-site clinical genetics consultations and gradually upgrading services to 502 children and young adults with ASD in their standard environment across 26 day-care hospitals and specialized institutions within the Greater Paris region. The evaluation included a clinical genetics consultation, screening for fragile X syndrome, metabolic workup, chromosomal microarray analysis, and, in a proportion of patients, next-generation sequencing of genes reported in ASD and other neurodevelopmental disorders. Results: Fragile X syndrome and pathogenic copy number variants (CNVs) accounted for the disease in 10% of cases, including 4/312 (1.3%) with fragile X syndrome and 34/388 (8.8%) with pathogenic CNVs (19 de novo and 4 inherited). Importantly, adding high-throughput resequencing of reported intellectual disability/ASD genes to the screening procedure had a major impact on diagnostic yield in the 141 patients examined most recently. Pathogenic or likely pathogenic sequence variants in 27 disease genes were identified in 33/141 patients (23.4%; 23 were de novo and 10 inherited, including five X-linked and five recessive compound heterozygous variants). Diagnosed cases presented atypical and/or syndromic ASD with moderate to severe intellectual disability. The diagnostic yield of fragile X syndrome and array CGH testing combined with next-generation sequencing was significantly higher than fragile X syndrome and array CGH alone (p value 0.009). No inborn errors of metabolism were detected with the metabolic screening. Conclusion: Based on the diagnostic rate observed in this cohort, we suggest that a stepwise procedure be considered, first screening pathogenic CNVs and a limited number of disease genes in a much larger number of patients, especially those with syndromic ASD and intellectual disability. En ligne : https://dx.doi.org/10.1186/s13229-019-0284-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Delayed M50/M100 evoked response component latency in minimally verbal/nonverbal children who have autism spectrum disorder / T. P. L. ROBERTS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 34 p. Titre : Delayed M50/M100 evoked response component latency in minimally verbal/nonverbal children who have autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : T. P. L. ROBERTS, Auteur ; J. MATSUZAKI, Auteur ; Lisa BLASKEY, Auteur ; Luke BLOY, Auteur ; J. C. EDGAR, Auteur ; M. KIM, Auteur ; M. KU, Auteur ; E. S. KUSCHNER, Auteur ; D. EMBICK, Auteur Article en page(s) : 34 p. Langues : Anglais (eng) Mots-clés : Auditory cortex  Autism spectrum disorder  M50/M100 responses and language impairment  Magnetoencephalography  Minimally verbal/non-verbal children  Nonverbal Index. décimale : PER Périodiques Résumé : Abnormal auditory neuromagnetic M50 and M100 responses, reflecting primary/secondary auditory cortex processing, have been reported in children who have autism spectrum disorder (ASD). Some studies have reported an association between delays in these responses and language impairment. However, as most prior research has focused on verbal individuals with ASD without cognitive impairment, rather little is known about neural activity during auditory processing in minimally verbal or nonverbal children who have ASD (ASD-MVNV)-children with little or no speech and often significant cognitive impairment. To understand the neurophysiological mechanisms underlying auditory processing in ASD-MVNV children, magnetoencephalography (MEG) measured M50 and M100 responses arising from left and right superior temporal gyri during tone stimuli in three cohorts: (1) MVNV children who have ASD (ASD-MVNV), (2) verbal children who have ASD and no intellectual disability (ASD-V), and (3) typically developing (TD) children. One hundred and five participants (8-12 years) were included in the final analyses (ASD-MVNV: n = 16, 9.85 +/- 1.32 years; ASD-V: n = 55, 10.64 +/- 1.31 years; TD: n = 34, 10.18 +/- 1.36 years). ASD-MVNV children showed significantly delayed M50 and M100 latencies compared to TD. These delays tended to be greater than the corresponding delays in verbal children with ASD. Across cohorts, delayed latencies were associated with language and communication skills, assessed by the Vineland Adaptive Behavior Scale Communication Domain. Findings suggest that auditory cortex neural activity measures could be dimensional objective indices of language impairment in ASD for either diagnostic (e.g., via threshold or cutoff) or prognostic (considering the continuous variable) use. En ligne : https://dx.doi.org/10.1186/s13229-019-0283-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Delayed M50/M100 evoked response component latency in minimally verbal/nonverbal children who have autism spectrum disorder [Texte imprimé et/ou numérique] / T. P. L. ROBERTS, Auteur ; J. MATSUZAKI, Auteur ; Lisa BLASKEY, Auteur ; Luke BLOY, Auteur ; J. C. EDGAR, Auteur ; M. KIM, Auteur ; M. KU, Auteur ; E. S. KUSCHNER, Auteur ; D. EMBICK, Auteur . - 34 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 34 p. Mots-clés : Auditory cortex  Autism spectrum disorder  M50/M100 responses and language impairment  Magnetoencephalography  Minimally verbal/non-verbal children  Nonverbal Index. décimale : PER Périodiques Résumé : Abnormal auditory neuromagnetic M50 and M100 responses, reflecting primary/secondary auditory cortex processing, have been reported in children who have autism spectrum disorder (ASD). Some studies have reported an association between delays in these responses and language impairment. However, as most prior research has focused on verbal individuals with ASD without cognitive impairment, rather little is known about neural activity during auditory processing in minimally verbal or nonverbal children who have ASD (ASD-MVNV)-children with little or no speech and often significant cognitive impairment. To understand the neurophysiological mechanisms underlying auditory processing in ASD-MVNV children, magnetoencephalography (MEG) measured M50 and M100 responses arising from left and right superior temporal gyri during tone stimuli in three cohorts: (1) MVNV children who have ASD (ASD-MVNV), (2) verbal children who have ASD and no intellectual disability (ASD-V), and (3) typically developing (TD) children. One hundred and five participants (8-12 years) were included in the final analyses (ASD-MVNV: n = 16, 9.85 +/- 1.32 years; ASD-V: n = 55, 10.64 +/- 1.31 years; TD: n = 34, 10.18 +/- 1.36 years). ASD-MVNV children showed significantly delayed M50 and M100 latencies compared to TD. These delays tended to be greater than the corresponding delays in verbal children with ASD. Across cohorts, delayed latencies were associated with language and communication skills, assessed by the Vineland Adaptive Behavior Scale Communication Domain. Findings suggest that auditory cortex neural activity measures could be dimensional objective indices of language impairment in ASD for either diagnostic (e.g., via threshold or cutoff) or prognostic (considering the continuous variable) use. En ligne : https://dx.doi.org/10.1186/s13229-019-0283-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism / H. G. KIM in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 35 p. Titre : Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism Type de document : Texte imprimé et/ou numérique Auteurs : H. G. KIM, Auteur ; J. A. ROSENFELD, Auteur ; D. A. SCOTT, Auteur ; G. BENEDICTE, Auteur ; J. D. LABONNE, Auteur ; J. BROWN, Auteur ; M. MCGUIRE, Auteur ; S. MAHIDA, Auteur ; S. NAIDU, Auteur ; J. GUTIERREZ, Auteur ; G. LESCA, Auteur ; V. DES PORTES, Auteur ; A. L. BRUEL, Auteur ; A. SORLIN, Auteur ; F. XIA, Auteur ; Y. CAPRI, Auteur ; E. MULLER, Auteur ; D. MCKNIGHT, Auteur ; E. TORTI, Auteur ; F. RUSCHENDORF, Auteur ; O. HUMMEL, Auteur ; Z. ISLAM, Auteur ; P. R. KOLATKAR, Auteur ; L. C. LAYMAN, Auteur ; D. RYU, Auteur ; I. K. KONG, Auteur ; S. MADAN-KHETARPAL, Auteur ; C. H. KIM, Auteur Article en page(s) : 35 p. Langues : Anglais (eng) Mots-clés : AT Hook domain  Autism spectrum disorder (ASD)  Bhc80  Intellectual disability (ID)  Intrinsically disordered region (IDR)  Kdm1a  Neurodevelopmental disorders  Phf21a  Potocki-Shaffer syndrome (PSS) Index. décimale : PER Périodiques Résumé : Background: PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 and its disruption in three patients with balanced translocations. In addition, three patients with de novo truncating mutations in PHF21A were reported recently. Here, we analyze genomic data from seven unrelated individuals with mutations in PHF21A and provide detailed clinical descriptions, further expanding the phenotype associated with PHF21A haploinsufficiency. Methods: Diagnostic trio whole exome sequencing, Sanger sequencing, use of GeneMatcher, targeted gene panel sequencing, and MiSeq sequencing techniques were used to identify and confirm variants. RT-qPCR was used to measure the normal expression pattern of PHF21A in multiple human tissues including 13 different brain tissues. Protein-DNA modeling was performed to substantiate the pathogenicity of the missense mutation. Results: We have identified seven heterozygous coding mutations, among which six are de novo (not maternal in one). Mutations include four frameshifts, one nonsense mutation in two patients, and one heterozygous missense mutation in the AT Hook domain, predicted to be deleterious and likely to cause loss of PHF21A function. We also found a new C-terminal domain composed of an intrinsically disordered region. This domain is truncated in six patients and thus likely to play an important role in the function of PHF21A, suggesting that haploinsufficiency is the likely underlying mechanism in the phenotype of seven patients. Our results extend the phenotypic spectrum of PHF21A mutations by adding autism spectrum disorder, epilepsy, hypotonia, and neurobehavioral problems. Furthermore, PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. Conclusion: Deleterious nonsense, frameshift, and missense mutations disrupting the AT Hook domain and/or an intrinsically disordered region in PHF21A were found to be associated with autism spectrum disorder, epilepsy, hypotonia, neurobehavioral problems, tapering fingers, clinodactyly, and syndactyly, in addition to intellectual disability and craniofacial anomalies. This suggests that PHF21A is involved in autism spectrum disorder and intellectual disability, and its haploinsufficiency causes a diverse neurological phenotype. En ligne : https://dx.doi.org/10.1186/s13229-019-0286-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism [Texte imprimé et/ou numérique] / H. G. KIM, Auteur ; J. A. ROSENFELD, Auteur ; D. A. SCOTT, Auteur ; G. BENEDICTE, Auteur ; J. D. LABONNE, Auteur ; J. BROWN, Auteur ; M. MCGUIRE, Auteur ; S. MAHIDA, Auteur ; S. NAIDU, Auteur ; J. GUTIERREZ, Auteur ; G. LESCA, Auteur ; V. DES PORTES, Auteur ; A. L. BRUEL, Auteur ; A. SORLIN, Auteur ; F. XIA, Auteur ; Y. CAPRI, Auteur ; E. MULLER, Auteur ; D. MCKNIGHT, Auteur ; E. TORTI, Auteur ; F. RUSCHENDORF, Auteur ; O. HUMMEL, Auteur ; Z. ISLAM, Auteur ; P. R. KOLATKAR, Auteur ; L. C. LAYMAN, Auteur ; D. RYU, Auteur ; I. K. KONG, Auteur ; S. MADAN-KHETARPAL, Auteur ; C. H. KIM, Auteur . - 35 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 35 p. Mots-clés : AT Hook domain  Autism spectrum disorder (ASD)  Bhc80  Intellectual disability (ID)  Intrinsically disordered region (IDR)  Kdm1a  Neurodevelopmental disorders  Phf21a  Potocki-Shaffer syndrome (PSS) Index. décimale : PER Périodiques Résumé : Background: PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 and its disruption in three patients with balanced translocations. In addition, three patients with de novo truncating mutations in PHF21A were reported recently. Here, we analyze genomic data from seven unrelated individuals with mutations in PHF21A and provide detailed clinical descriptions, further expanding the phenotype associated with PHF21A haploinsufficiency. Methods: Diagnostic trio whole exome sequencing, Sanger sequencing, use of GeneMatcher, targeted gene panel sequencing, and MiSeq sequencing techniques were used to identify and confirm variants. RT-qPCR was used to measure the normal expression pattern of PHF21A in multiple human tissues including 13 different brain tissues. Protein-DNA modeling was performed to substantiate the pathogenicity of the missense mutation. Results: We have identified seven heterozygous coding mutations, among which six are de novo (not maternal in one). Mutations include four frameshifts, one nonsense mutation in two patients, and one heterozygous missense mutation in the AT Hook domain, predicted to be deleterious and likely to cause loss of PHF21A function. We also found a new C-terminal domain composed of an intrinsically disordered region. This domain is truncated in six patients and thus likely to play an important role in the function of PHF21A, suggesting that haploinsufficiency is the likely underlying mechanism in the phenotype of seven patients. Our results extend the phenotypic spectrum of PHF21A mutations by adding autism spectrum disorder, epilepsy, hypotonia, and neurobehavioral problems. Furthermore, PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. Conclusion: Deleterious nonsense, frameshift, and missense mutations disrupting the AT Hook domain and/or an intrinsically disordered region in PHF21A were found to be associated with autism spectrum disorder, epilepsy, hypotonia, neurobehavioral problems, tapering fingers, clinodactyly, and syndactyly, in addition to intellectual disability and craniofacial anomalies. This suggests that PHF21A is involved in autism spectrum disorder and intellectual disability, and its haploinsufficiency causes a diverse neurological phenotype. En ligne : https://dx.doi.org/10.1186/s13229-019-0286-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood / C. E. MORDAUNT in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 36 p. Titre : A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood Type de document : Texte imprimé et/ou numérique Auteurs : C. E. MORDAUNT, Auteur ; B. Y. PARK, Auteur ; K. M. BAKULSKI, Auteur ; J. I. FEINBERG, Auteur ; Lisa A. CROEN, Auteur ; Christine LADD-ACOSTA, Auteur ; C. J. NEWSCHAFFER, Auteur ; Heather E. VOLK, Auteur ; S. OZONOFF, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur ; Rebecca J. SCHMIDT, Auteur ; M. D. FALLIN, Auteur Article en page(s) : 36 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Chromatin  Environment  Gene expression  Meta-analysis  Microarray  Neurodevelopment  Perinatal  Prospective study  Umbilical cord blood Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology. En ligne : http://dx.doi.org/10.1186/s13229-019-0287-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood [Texte imprimé et/ou numérique] / C. E. MORDAUNT, Auteur ; B. Y. PARK, Auteur ; K. M. BAKULSKI, Auteur ; J. I. FEINBERG, Auteur ; Lisa A. CROEN, Auteur ; Christine LADD-ACOSTA, Auteur ; C. J. NEWSCHAFFER, Auteur ; Heather E. VOLK, Auteur ; S. OZONOFF, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur ; Rebecca J. SCHMIDT, Auteur ; M. D. FALLIN, Auteur . - 36 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 36 p. Mots-clés : Autism spectrum disorder  Chromatin  Environment  Gene expression  Meta-analysis  Microarray  Neurodevelopment  Perinatal  Prospective study  Umbilical cord blood Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology. En ligne : http://dx.doi.org/10.1186/s13229-019-0287-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome / J. FROHLICH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 37 p. Titre : Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. FROHLICH, Auteur ; L. T. REITER, Auteur ; V. SARAVANAPANDIAN, Auteur ; C. DISTEFANO, Auteur ; S. HUBERTY, Auteur ; C. HYDE, Auteur ; S. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; P. GOLSHANI, Auteur ; A. IRIMIA, Auteur ; R. W. OLSEN, Auteur ; J. F. HIPP, Auteur ; S. S. JESTE, Auteur Article en page(s) : 37 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-019-0280-6.]. En ligne : http://dx.doi.org/10.1186/s13229-019-0288-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome [Texte imprimé et/ou numérique] / J. FROHLICH, Auteur ; L. T. REITER, Auteur ; V. SARAVANAPANDIAN, Auteur ; C. DISTEFANO, Auteur ; S. HUBERTY, Auteur ; C. HYDE, Auteur ; S. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; P. GOLSHANI, Auteur ; A. IRIMIA, Auteur ; R. W. OLSEN, Auteur ; J. F. HIPP, Auteur ; S. S. JESTE, Auteur . - 37 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 37 p. Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-019-0280-6.]. En ligne : http://dx.doi.org/10.1186/s13229-019-0288-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation / A. SAFFARI in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 38 p. Titre : RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation Type de document : Texte imprimé et/ou numérique Auteurs : A. SAFFARI, Auteur ; M. ARNO, Auteur ; E. NASSER, Auteur ; A. RONALD, Auteur ; C. C. Y. WONG, Auteur ; Leonard C. SCHALKWYK, Auteur ; J. MILL, Auteur ; F. DUDBRIDGE, Auteur ; E. L. MEABURN, Auteur Article en page(s) : 38 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  DNA methylation  Discordance  Epigenomics  Gene expression  Immune  MZ twins  RNA-seq  Transcriptomics Index. décimale : PER Périodiques Résumé : Background: A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC. Methods: Genome-wide gene expression data were generated using RNA-seq on whole blood samples taken from 16 pairs of monozygotic (MZ) twins and seven twin pair members (39 individuals in total), who had been assessed for ASC and autism traits at age 12. Differential expression (DE) analyses were performed between (a) affected and unaffected subjects (N = 36) and (b) within discordant ASC MZ twin pairs (total N = 11) to identify environmental-driven DE. Gene set enrichment and pathway testing was performed on DE gene lists. Finally, an integrative analysis using DNA methylation data aimed to identify genes with consistent evidence for altered regulation in cis. Results: In the discordant twin analysis, three genes showed evidence for DE at FDR < 10%: IGHG4, EVI2A and SNORD15B. In the case-control analysis, four DE genes were identified at FDR < 10% including IGHG4, PRR13P5, DEPDC1B, and ZNF501. We find enrichment for DE of genes curated in the SFARI human gene database. Pathways showing evidence of enrichment included those related to immune cell signalling and immune response, transcriptional control and cell cycle/proliferation. Integrative methylomic and transcriptomic analysis identified a number of genes showing suggestive evidence for cis dysregulation. Limitations: Identical twins stably discordant for ASC are rare, and as such the sample size was limited and constrained to the use of peripheral blood tissue for transcriptomic and methylomic profiling. Given these primary limitations, we focused on transcript-level analysis. Conclusions: Using a cohort of ASC discordant and concordant MZ twins, we add to the growing body of transcriptomic-based evidence for an immune-based component in the molecular aetiology of ASC. Whilst the sample size was limited, the study demonstrates the utility of the discordant MZ twin design combined with multi-omics integration for maximising the potential to identify disease-associated molecular signals. En ligne : http://dx.doi.org/10.1186/s13229-019-0285-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation [Texte imprimé et/ou numérique] / A. SAFFARI, Auteur ; M. ARNO, Auteur ; E. NASSER, Auteur ; A. RONALD, Auteur ; C. C. Y. WONG, Auteur ; Leonard C. SCHALKWYK, Auteur ; J. MILL, Auteur ; F. DUDBRIDGE, Auteur ; E. L. MEABURN, Auteur . - 38 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 38 p. Mots-clés : Autism spectrum disorder  DNA methylation  Discordance  Epigenomics  Gene expression  Immune  MZ twins  RNA-seq  Transcriptomics Index. décimale : PER Périodiques Résumé : Background: A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC. Methods: Genome-wide gene expression data were generated using RNA-seq on whole blood samples taken from 16 pairs of monozygotic (MZ) twins and seven twin pair members (39 individuals in total), who had been assessed for ASC and autism traits at age 12. Differential expression (DE) analyses were performed between (a) affected and unaffected subjects (N = 36) and (b) within discordant ASC MZ twin pairs (total N = 11) to identify environmental-driven DE. Gene set enrichment and pathway testing was performed on DE gene lists. Finally, an integrative analysis using DNA methylation data aimed to identify genes with consistent evidence for altered regulation in cis. Results: In the discordant twin analysis, three genes showed evidence for DE at FDR < 10%: IGHG4, EVI2A and SNORD15B. In the case-control analysis, four DE genes were identified at FDR < 10% including IGHG4, PRR13P5, DEPDC1B, and ZNF501. We find enrichment for DE of genes curated in the SFARI human gene database. Pathways showing evidence of enrichment included those related to immune cell signalling and immune response, transcriptional control and cell cycle/proliferation. Integrative methylomic and transcriptomic analysis identified a number of genes showing suggestive evidence for cis dysregulation. Limitations: Identical twins stably discordant for ASC are rare, and as such the sample size was limited and constrained to the use of peripheral blood tissue for transcriptomic and methylomic profiling. Given these primary limitations, we focused on transcript-level analysis. Conclusions: Using a cohort of ASC discordant and concordant MZ twins, we add to the growing body of transcriptomic-based evidence for an immune-based component in the molecular aetiology of ASC. Whilst the sample size was limited, the study demonstrates the utility of the discordant MZ twin design combined with multi-omics integration for maximising the potential to identify disease-associated molecular signals. En ligne : http://dx.doi.org/10.1186/s13229-019-0285-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Intact neural representations of affective meaning of touch but lack of embodied resonance in autism: a multi-voxel pattern analysis study / H. LEE MASSON in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 39 p. Titre : Intact neural representations of affective meaning of touch but lack of embodied resonance in autism: a multi-voxel pattern analysis study Type de document : Texte imprimé et/ou numérique Auteurs : H. LEE MASSON, Auteur ; I. PILLET, Auteur ; S. AMELYNCK, Auteur ; S. VAN DE PLAS, Auteur ; M. HENDRIKS, Auteur ; H. OP DE BEECK, Auteur ; Bart BOETS, Auteur Article en page(s) : 39 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Embodied simulation  Multi-voxel pattern analysis  Social touch aversion  Social touch observation  Theory of mind Index. décimale : PER Périodiques Résumé : Background: Humans can easily grasp the affective meaning of touch when observing social interactions. Several neural systems support this ability, including the theory of mind (ToM) network and the somatosensory system linked to embodied resonance, but it is unclear how these systems are affected in autism spectrum disorder (ASD). Individuals with ASD exhibit impairments in the use of nonverbal communication such as social and reciprocal touch. Despite the importance of touch in social communication and the reported touch aversion in ASD, surprisingly little is known about the neural systems underlying impairments in touch communication in ASD. Methods: The present study applies a dynamic and socially meaningful stimulus set combined with functional magnetic resonance imaging (fMRI) to pinpoint atypicalities in the neural circuitry underlying socio-affective touch observation in adults with ASD. Twenty-one adults with ASD and 21 matched neurotypical adults evaluated the valence and arousal of 75 video fragments displaying touch interactions. Subsequently, they underwent fMRI while watching the same videos. Using multi-voxel pattern analysis (MVPA) and multiple regression analysis, we examined which brain regions represent the socio-affective meaning of observed touch. To further understand the brain-behavior relationship, we correlated the strength of affective representations in the somatosensory cortex with individuals' attitude towards social touch in general and with a quantitative index of autism traits as measured by the Social Responsiveness Scale. Results: Results revealed that the affective meaning of touch was well represented in the temporoparietal junction, a core mentalizing area, in both groups. Conversely, only the neurotypical group represented affective touch in the somatosensory cortex, a region involved in self-experienced touch. Lastly, irrespective of the group, individuals with a more positive attitude towards receiving, witnessing, and providing social touch and with a higher score on social responsivity showed more differentiated representations of the affective meaning of touch in these somatosensory areas. Conclusions: Together, our findings imply that male adults with ASD show intact cognitive understanding (i.e., "knowing") of observed socio-affective touch interactions, but lack of spontaneous embodied resonance (i.e., "feeling"). En ligne : http://dx.doi.org/10.1186/s13229-019-0294-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Intact neural representations of affective meaning of touch but lack of embodied resonance in autism: a multi-voxel pattern analysis study [Texte imprimé et/ou numérique] / H. LEE MASSON, Auteur ; I. PILLET, Auteur ; S. AMELYNCK, Auteur ; S. VAN DE PLAS, Auteur ; M. HENDRIKS, Auteur ; H. OP DE BEECK, Auteur ; Bart BOETS, Auteur . - 39 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 39 p. Mots-clés : Autism spectrum disorder  Embodied simulation  Multi-voxel pattern analysis  Social touch aversion  Social touch observation  Theory of mind Index. décimale : PER Périodiques Résumé : Background: Humans can easily grasp the affective meaning of touch when observing social interactions. Several neural systems support this ability, including the theory of mind (ToM) network and the somatosensory system linked to embodied resonance, but it is unclear how these systems are affected in autism spectrum disorder (ASD). Individuals with ASD exhibit impairments in the use of nonverbal communication such as social and reciprocal touch. Despite the importance of touch in social communication and the reported touch aversion in ASD, surprisingly little is known about the neural systems underlying impairments in touch communication in ASD. Methods: The present study applies a dynamic and socially meaningful stimulus set combined with functional magnetic resonance imaging (fMRI) to pinpoint atypicalities in the neural circuitry underlying socio-affective touch observation in adults with ASD. Twenty-one adults with ASD and 21 matched neurotypical adults evaluated the valence and arousal of 75 video fragments displaying touch interactions. Subsequently, they underwent fMRI while watching the same videos. Using multi-voxel pattern analysis (MVPA) and multiple regression analysis, we examined which brain regions represent the socio-affective meaning of observed touch. To further understand the brain-behavior relationship, we correlated the strength of affective representations in the somatosensory cortex with individuals' attitude towards social touch in general and with a quantitative index of autism traits as measured by the Social Responsiveness Scale. Results: Results revealed that the affective meaning of touch was well represented in the temporoparietal junction, a core mentalizing area, in both groups. Conversely, only the neurotypical group represented affective touch in the somatosensory cortex, a region involved in self-experienced touch. Lastly, irrespective of the group, individuals with a more positive attitude towards receiving, witnessing, and providing social touch and with a higher score on social responsivity showed more differentiated representations of the affective meaning of touch in these somatosensory areas. Conclusions: Together, our findings imply that male adults with ASD show intact cognitive understanding (i.e., "knowing") of observed socio-affective touch interactions, but lack of spontaneous embodied resonance (i.e., "feeling"). En ligne : http://dx.doi.org/10.1186/s13229-019-0294-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

The Friendship Questionnaire, autism, and gender differences: a study revisited / F. SEDGEWICK in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 40 p. Titre : The Friendship Questionnaire, autism, and gender differences: a study revisited Type de document : Texte imprimé et/ou numérique Auteurs : F. SEDGEWICK, Auteur ; J. LEPPANEN, Auteur ; K. TCHANTURIA, Auteur Article en page(s) : 40 p. Langues : Anglais (eng) Mots-clés : Autism  Friendship  Gender  Non-binary  Relationship  Social communication Index. décimale : PER Périodiques Résumé : Background: The Friendship Questionnaire (FQ) is a widely used measure of friendships in autism research and beyond. This study sought to revisit the original paper where the measure was presented, using a larger sample of both autistic and non-autistic participants to examine gender differences in scoring. It also sought to expand upon the original paper by comparing FQ results to those of the Unidimensional Relationship Closeness Scale (URCS), to examine whether there are differences in how autistic people report on their general friendships in contrast to their most significant relationships. Methods: Participants were recruited for an online study, and 949 people (532 autistic, 417 non-autistic) aged between 18 and 81 took part. Participants completed a demographic questionnaire, the Autism Quotient-28, the Friendship Questionnaire, and the Unidimensional Relationship Closeness Scale. Results: We used robust regressions and Pearson's correlational analyses, conducted in R. Autistic people scored lower than non-autistic people on the FQ, and similar gender differences in the pattern of FQ scores were seen in both groups. There was a significant negative correlation between AQ and FQ scores in both groups. On the URCS, we took the data from those who rated specific close relationships and found that autistic people scored this relationship more highly than non-autistic adults did. There was a significant negative correlation between AQ and URCS scores in both groups. Also, in both groups, there was a significant positive correlation between FQ and URCS scores. Limitations: The data is entirely self-report, and diagnoses could not be verified with a clinician, although AQ scores support self-identification as autistic. Also, the groups were not evenly matched on age and other demographic variables, although this was controlled for in analyses. It is also the case that more autistic than non-autistic people were unable to specify a close relationship to score on the URCS, meaning that a certain set of experiences are not represented in this data. Conclusions: We conclude that our data replicates the core finding of the original FQ paper that autistic people score lower on the FQ. In contrast to that paper, however, we found that there were gender differences among the autistic population. Also, our inclusion of the URCS suggests that the intimate romantic relationships and best-friendships of autistic people can be of similar quality to those of non-autistic people, suggesting that there may be important differences in autistic people's relations with friends in general versus close friends and romantic partners. En ligne : http://dx.doi.org/10.1186/s13229-019-0295-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] The Friendship Questionnaire, autism, and gender differences: a study revisited [Texte imprimé et/ou numérique] / F. SEDGEWICK, Auteur ; J. LEPPANEN, Auteur ; K. TCHANTURIA, Auteur . - 40 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 40 p. Mots-clés : Autism  Friendship  Gender  Non-binary  Relationship  Social communication Index. décimale : PER Périodiques Résumé : Background: The Friendship Questionnaire (FQ) is a widely used measure of friendships in autism research and beyond. This study sought to revisit the original paper where the measure was presented, using a larger sample of both autistic and non-autistic participants to examine gender differences in scoring. It also sought to expand upon the original paper by comparing FQ results to those of the Unidimensional Relationship Closeness Scale (URCS), to examine whether there are differences in how autistic people report on their general friendships in contrast to their most significant relationships. Methods: Participants were recruited for an online study, and 949 people (532 autistic, 417 non-autistic) aged between 18 and 81 took part. Participants completed a demographic questionnaire, the Autism Quotient-28, the Friendship Questionnaire, and the Unidimensional Relationship Closeness Scale. Results: We used robust regressions and Pearson's correlational analyses, conducted in R. Autistic people scored lower than non-autistic people on the FQ, and similar gender differences in the pattern of FQ scores were seen in both groups. There was a significant negative correlation between AQ and FQ scores in both groups. On the URCS, we took the data from those who rated specific close relationships and found that autistic people scored this relationship more highly than non-autistic adults did. There was a significant negative correlation between AQ and URCS scores in both groups. Also, in both groups, there was a significant positive correlation between FQ and URCS scores. Limitations: The data is entirely self-report, and diagnoses could not be verified with a clinician, although AQ scores support self-identification as autistic. Also, the groups were not evenly matched on age and other demographic variables, although this was controlled for in analyses. It is also the case that more autistic than non-autistic people were unable to specify a close relationship to score on the URCS, meaning that a certain set of experiences are not represented in this data. Conclusions: We conclude that our data replicates the core finding of the original FQ paper that autistic people score lower on the FQ. In contrast to that paper, however, we found that there were gender differences among the autistic population. Also, our inclusion of the URCS suggests that the intimate romantic relationships and best-friendships of autistic people can be of similar quality to those of non-autistic people, suggesting that there may be important differences in autistic people's relations with friends in general versus close friends and romantic partners. En ligne : http://dx.doi.org/10.1186/s13229-019-0295-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons / I. TONAZZINI in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 41 p. Titre : The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons Type de document : Texte imprimé et/ou numérique Auteurs : I. TONAZZINI, Auteur ; G. M. VAN WOERDEN, Auteur ; C. MASCIULLO, Auteur ; E. J. MIENTJES, Auteur ; Y. ELGERSMA, Auteur ; M. CECCHINI, Auteur Article en page(s) : 41 p. Langues : Anglais (eng) Mots-clés : 15q duplication autism  Angelman syndrome  Axonal guidance  Contact guidance  Cytoskeleton  Microgratings  Nocodazole  Ubiquitin ligase E3a (UBE3A) Index. décimale : PER Périodiques Résumé : Background: Although neuronal extracellular sensing is emerging as crucial for brain wiring and therefore plasticity, little is known about these processes in neurodevelopmental disorders. Ubiquitin protein ligase E3A (UBE3A) plays a key role in neurodevelopment. Lack of UBE3A leads to Angelman syndrome (AS), while its increase is among the most prevalent genetic causes of autism (e.g., Dup15q syndrome). By using microstructured substrates that can induce specific directional stimuli in cells, we previously found deficient topographical contact guidance in AS neurons, which was linked to a dysregulated activation of the focal adhesion pathway. Methods: Here, we study axon and dendrite contact guidance and neuronal morphological features of wild-type, AS, and UBE3A-overexpressing neurons (Dup15q autism model) on micrograting substrates, with the aim to clarify the role of UBE3A in neuronal guidance. Results: We found that loss of axonal contact guidance is specific for AS neurons while UBE3A overexpression does not affect neuronal directional polarization along microgratings. Deficits at the level of axonal branching, growth cone orientation and actin fiber content, focal adhesion (FA) effectors, and actin fiber-binding proteins were observed in AS neurons. We tested different rescue strategies for restoring correct topographical guidance in AS neurons on microgratings, by either UBE3A protein re-expression or by pharmacological treatments acting on cytoskeleton contractility. Nocodazole, a drug that depolymerizes microtubules and increases cell contractility, rescued AS axonal alignment to the gratings by partially restoring focal adhesion pathway activation. Surprisingly, UBE3A re-expression only resulted in partial rescue of the phenotype. Conclusions: We identified a specific in vitro deficit in axonal topographical guidance due selectively to the loss of UBE3A, and we further demonstrate that this defective guidance can be rescued to a certain extent by pharmacological or genetic treatment strategies. Overall, cytoskeleton dynamics emerge as important partners in UBE3A-mediated contact guidance responses. These results support the view that UBE3A-related deficits in early neuronal morphogenesis may lead to defective neuronal connectivity and plasticity. En ligne : http://dx.doi.org/10.1186/s13229-019-0293-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons [Texte imprimé et/ou numérique] / I. TONAZZINI, Auteur ; G. M. VAN WOERDEN, Auteur ; C. MASCIULLO, Auteur ; E. J. MIENTJES, Auteur ; Y. ELGERSMA, Auteur ; M. CECCHINI, Auteur . - 41 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 41 p. Mots-clés : 15q duplication autism  Angelman syndrome  Axonal guidance  Contact guidance  Cytoskeleton  Microgratings  Nocodazole  Ubiquitin ligase E3a (UBE3A) Index. décimale : PER Périodiques Résumé : Background: Although neuronal extracellular sensing is emerging as crucial for brain wiring and therefore plasticity, little is known about these processes in neurodevelopmental disorders. Ubiquitin protein ligase E3A (UBE3A) plays a key role in neurodevelopment. Lack of UBE3A leads to Angelman syndrome (AS), while its increase is among the most prevalent genetic causes of autism (e.g., Dup15q syndrome). By using microstructured substrates that can induce specific directional stimuli in cells, we previously found deficient topographical contact guidance in AS neurons, which was linked to a dysregulated activation of the focal adhesion pathway. Methods: Here, we study axon and dendrite contact guidance and neuronal morphological features of wild-type, AS, and UBE3A-overexpressing neurons (Dup15q autism model) on micrograting substrates, with the aim to clarify the role of UBE3A in neuronal guidance. Results: We found that loss of axonal contact guidance is specific for AS neurons while UBE3A overexpression does not affect neuronal directional polarization along microgratings. Deficits at the level of axonal branching, growth cone orientation and actin fiber content, focal adhesion (FA) effectors, and actin fiber-binding proteins were observed in AS neurons. We tested different rescue strategies for restoring correct topographical guidance in AS neurons on microgratings, by either UBE3A protein re-expression or by pharmacological treatments acting on cytoskeleton contractility. Nocodazole, a drug that depolymerizes microtubules and increases cell contractility, rescued AS axonal alignment to the gratings by partially restoring focal adhesion pathway activation. Surprisingly, UBE3A re-expression only resulted in partial rescue of the phenotype. Conclusions: We identified a specific in vitro deficit in axonal topographical guidance due selectively to the loss of UBE3A, and we further demonstrate that this defective guidance can be rescued to a certain extent by pharmacological or genetic treatment strategies. Overall, cytoskeleton dynamics emerge as important partners in UBE3A-mediated contact guidance responses. These results support the view that UBE3A-related deficits in early neuronal morphogenesis may lead to defective neuronal connectivity and plasticity. En ligne : http://dx.doi.org/10.1186/s13229-019-0293-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference / R. H. C. NORRIS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 42 p. Titre : Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference Type de document : Texte imprimé et/ou numérique Auteurs : R. H. C. NORRIS, Auteur ; L. CHURILOV, Auteur ; A. J. HANNAN, Auteur ; J. NITHIANANTHARAJAH, Auteur Article en page(s) : 42 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Perseveration  Processing speed  Reaction time  Synapse Index. décimale : PER Périodiques Résumé : Cognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models of Nlgn3 dysfunction (Nlgn3 (-/y) and Nlgn3 (R451C)). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations in Nlgn3 do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms. En ligne : http://dx.doi.org/10.1186/s13229-019-0292-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference [Texte imprimé et/ou numérique] / R. H. C. NORRIS, Auteur ; L. CHURILOV, Auteur ; A. J. HANNAN, Auteur ; J. NITHIANANTHARAJAH, Auteur . - 42 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 42 p. Mots-clés : Autism spectrum disorder  Perseveration  Processing speed  Reaction time  Synapse Index. décimale : PER Périodiques Résumé : Cognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models of Nlgn3 dysfunction (Nlgn3 (-/y) and Nlgn3 (R451C)). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations in Nlgn3 do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms. En ligne : http://dx.doi.org/10.1186/s13229-019-0292-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Autism and family involvement in the right to education in the EU: policy mapping in the Netherlands, Belgium and Germany / R. VAN KESSEL in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 43 p. Titre : Autism and family involvement in the right to education in the EU: policy mapping in the Netherlands, Belgium and Germany Type de document : Texte imprimé et/ou numérique Auteurs : R. VAN KESSEL, Auteur ; A. ROMAN-URRESTARAZU, Auteur ; A. RUIGROK, Auteur ; R. HOLT, Auteur ; M. COMMERS, Auteur ; R. A. HOEKSTRA, Auteur ; K. CZABANOWSKA, Auteur ; Carol BRAYNE, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 43 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Introduction: In recent years, the universal right to education has been emphasised by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies relevant to special education needs and parental involvement of children with autism at an international level and in the Netherlands, Germany and Belgium. Methods: A policy path analysis was performed using a scoping review as an underlying methodological framework. This allowed for a rapid gathering of available data from which a timeline of adopted policies was derived. Results and discussion: Internationally, the universal right to education has been reinforced repeatedly and the values of the Universal Declaration of Human Rights have been reiterated with every reinforcement. Also, the additional support that a child with special education needs requires is acknowledged and measures are taken to facilitate access to any education for all children. There are slight cross-country differences between the countries under study, attributable to differences in national regulation of education. However, all countries have progressed to a state where the right to education for all children is integrated on a policy level and measures are taken to enable children with special needs to participate in education. Recently, an attempt to implement a form of inclusive education was made as a form of special needs provision. Nevertheless, nowhere has this been implemented successfully yet. Conclusion: The Universal Declaration of Human Rights was a critical juncture in international policy and created an environment where the universal right to education has been implemented for all children in the countries under study. En ligne : http://dx.doi.org/10.1186/s13229-019-0297-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Autism and family involvement in the right to education in the EU: policy mapping in the Netherlands, Belgium and Germany [Texte imprimé et/ou numérique] / R. VAN KESSEL, Auteur ; A. ROMAN-URRESTARAZU, Auteur ; A. RUIGROK, Auteur ; R. HOLT, Auteur ; M. COMMERS, Auteur ; R. A. HOEKSTRA, Auteur ; K. CZABANOWSKA, Auteur ; Carol BRAYNE, Auteur ; Simon BARON-COHEN, Auteur . - 43 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 43 p. Index. décimale : PER Périodiques Résumé : Introduction: In recent years, the universal right to education has been emphasised by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies relevant to special education needs and parental involvement of children with autism at an international level and in the Netherlands, Germany and Belgium. Methods: A policy path analysis was performed using a scoping review as an underlying methodological framework. This allowed for a rapid gathering of available data from which a timeline of adopted policies was derived. Results and discussion: Internationally, the universal right to education has been reinforced repeatedly and the values of the Universal Declaration of Human Rights have been reiterated with every reinforcement. Also, the additional support that a child with special education needs requires is acknowledged and measures are taken to facilitate access to any education for all children. There are slight cross-country differences between the countries under study, attributable to differences in national regulation of education. However, all countries have progressed to a state where the right to education for all children is integrated on a policy level and measures are taken to enable children with special needs to participate in education. Recently, an attempt to implement a form of inclusive education was made as a form of special needs provision. Nevertheless, nowhere has this been implemented successfully yet. Conclusion: The Universal Declaration of Human Rights was a critical juncture in international policy and created an environment where the universal right to education has been implemented for all children in the countries under study. En ligne : http://dx.doi.org/10.1186/s13229-019-0297-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Reproductive stoppage in autism spectrum disorder in a population of 2.5 million individuals / R. KUJA-HALKOLA in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 45 p. Titre : Reproductive stoppage in autism spectrum disorder in a population of 2.5 million individuals Type de document : Texte imprimé et/ou numérique Auteurs : R. KUJA-HALKOLA, Auteur ; H. LARSSON, Auteur ; S. LUNDSTRÖM, Auteur ; S. SANDIN, Auteur ; A. CHIZARIFARD, Auteur ; Sven BÖLTE, Auteur ; P. LICHTENSTEIN, Auteur ; E. FRANS, Auteur Article en page(s) : 45 p. Langues : Anglais (eng) Mots-clés : Autism  Autism spectrum disorder  Fecundity  Reproduction  Reproductive stoppage Index. décimale : PER Périodiques Résumé : Background: It has been suggested that parents of children with autism spectrum disorder (ASD) curtail their reproduction, a phenomenon known as reproductive stoppage. To investigate the presence of reproductive stoppage, we followed the reproduction in mothers of children with or without an ASD diagnosis using Swedish population-based registries. Methods: We followed all families with first child born in 1987 or later. In total 2,521,103 children, nested within 1,270,017 mothers, were included. Exposure was presence of ASD diagnosis in earlier born siblings, and outcome was considered as (1) inter-pregnancy interval and (2) number of subsequent children. Results: Analyses of inter-pregnancy intervals showed that the association differed across birth orders, with a lower rate of second children when first child had ASD diagnosis, but an increased rate of third and higher birth orders in families where a previous child had an ASD diagnosis. When all birth orders were simultaneously considered, families with a child with an ASD diagnosis were less likely to have another child (hazard ratio (HR), 0.79; 95% confidence interval [95% CI], 0.78-0.80). However, when adjusted for birth order, the association was close to null (HR, 0.97; 95% CI, 0.96-0.99), and after additional adjustments (maternal age, birth period, sex, paternal age, and maternal education), the association disappeared (HR, 1.00; 95% CI, 0.99-1.02). In analyses of subsequent children, after adjustment for covariates, families with an ASD diagnosis had 4% more subsequent children (rate ratio, 1.04; 95% CI, 1.03-1.05). Limitations: The study was undertaken in a country with largely tax-funded healthcare; results may not generalize to other societies. Following the current dominating umbrella concept of ASD, we did not differentiate between the ASD sub-diagnoses; it is possible that reproductive patterns can be dependent on ASD subtypes and the severity and composition of ASD phenotypes and comorbidities. Conclusions: This study does not support a universal reproductive stoppage effect in ASD families, when birth order and other factors are considered. Therefore, proper attention to birth order and other factors may alleviate potential bias in familial aggregation studies of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0300-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Reproductive stoppage in autism spectrum disorder in a population of 2.5 million individuals [Texte imprimé et/ou numérique] / R. KUJA-HALKOLA, Auteur ; H. LARSSON, Auteur ; S. LUNDSTRÖM, Auteur ; S. SANDIN, Auteur ; A. CHIZARIFARD, Auteur ; Sven BÖLTE, Auteur ; P. LICHTENSTEIN, Auteur ; E. FRANS, Auteur . - 45 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 45 p. Mots-clés : Autism  Autism spectrum disorder  Fecundity  Reproduction  Reproductive stoppage Index. décimale : PER Périodiques Résumé : Background: It has been suggested that parents of children with autism spectrum disorder (ASD) curtail their reproduction, a phenomenon known as reproductive stoppage. To investigate the presence of reproductive stoppage, we followed the reproduction in mothers of children with or without an ASD diagnosis using Swedish population-based registries. Methods: We followed all families with first child born in 1987 or later. In total 2,521,103 children, nested within 1,270,017 mothers, were included. Exposure was presence of ASD diagnosis in earlier born siblings, and outcome was considered as (1) inter-pregnancy interval and (2) number of subsequent children. Results: Analyses of inter-pregnancy intervals showed that the association differed across birth orders, with a lower rate of second children when first child had ASD diagnosis, but an increased rate of third and higher birth orders in families where a previous child had an ASD diagnosis. When all birth orders were simultaneously considered, families with a child with an ASD diagnosis were less likely to have another child (hazard ratio (HR), 0.79; 95% confidence interval [95% CI], 0.78-0.80). However, when adjusted for birth order, the association was close to null (HR, 0.97; 95% CI, 0.96-0.99), and after additional adjustments (maternal age, birth period, sex, paternal age, and maternal education), the association disappeared (HR, 1.00; 95% CI, 0.99-1.02). In analyses of subsequent children, after adjustment for covariates, families with an ASD diagnosis had 4% more subsequent children (rate ratio, 1.04; 95% CI, 1.03-1.05). Limitations: The study was undertaken in a country with largely tax-funded healthcare; results may not generalize to other societies. Following the current dominating umbrella concept of ASD, we did not differentiate between the ASD sub-diagnoses; it is possible that reproductive patterns can be dependent on ASD subtypes and the severity and composition of ASD phenotypes and comorbidities. Conclusions: This study does not support a universal reproductive stoppage effect in ASD families, when birth order and other factors are considered. Therefore, proper attention to birth order and other factors may alleviate potential bias in familial aggregation studies of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0300-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Familiality of behavioral flexibility and response inhibition deficits in autism spectrum disorder (ASD) / Lauren M. SCHMITT in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 47 p. Titre : Familiality of behavioral flexibility and response inhibition deficits in autism spectrum disorder (ASD) Type de document : Texte imprimé et/ou numérique Auteurs : Lauren M. SCHMITT, Auteur ; E. K. BOJANEK, Auteur ; S. P. WHITE, Auteur ; M. E. RAGOZZINO, Auteur ; Edwin H. Jr COOK, Auteur ; J. A. SWEENEY, Auteur ; M. W. MOSCONI, Auteur Article en page(s) : 47 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background: Diminished cognitive control, including reduced behavioral flexibility and behavioral response inhibition, has been repeatedly documented in autism spectrum disorder (ASD). We evaluated behavioral flexibility and response inhibition in probands and their parents using a family trio design to determine the extent to which these cognitive control impairments represent familial traits associated with ASD. Methods: We examined 66 individuals with ASD (probands), 135 unaffected biological parents, and 76 typically developing controls. Participants completed a probabilistic reversal learning task (PRL) and a stop-signal task (SST) to assess behavioral flexibility and response inhibition respectively. Rates of PRL and SST errors were examined across groups, within families, and in relation to clinical and subclinical traits of ASD. Based on prior findings that subclinical broader autism phenotypic (BAP) traits may co-segregate within families and reflect heritable risk factors, we also examined whether cognitive control deficits were more prominent in families in which parents showed BAP features (BAP+). Results: Probands and parents each showed increased rates of PRL and SST errors relative to controls. Error rates across tasks were not related. SST error rates inter-correlated among probands and their parents. PRL errors were more severe in BAP+ parents and their children relative to BAP- parents and their children. For probands of BAP+ parents, PRL and SST error rates were associated with more severe social-communication abnormalities and repetitive behaviors, respectively. Conclusion: Reduced behavioral flexibility and response inhibition are present among probands and their unaffected parents, but represent unique familial deficits associated with ASD that track with separate clinical issues. Specifically, behavioral response inhibition impairments are familial in ASD and manifest independently from parental subclinical features. In contrast, behavioral flexibility deficits are selectively present in families with BAP characteristics, suggesting they co-segregate in families with parental subclinical social, communication, and rigid personality traits. Together, these findings provide evidence that behavioral flexibility and response inhibition impairments track differentially with ASD risk mechanisms and related behavioral traits. En ligne : http://dx.doi.org/10.1186/s13229-019-0296-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Familiality of behavioral flexibility and response inhibition deficits in autism spectrum disorder (ASD) [Texte imprimé et/ou numérique] / Lauren M. SCHMITT, Auteur ; E. K. BOJANEK, Auteur ; S. P. WHITE, Auteur ; M. E. RAGOZZINO, Auteur ; Edwin H. Jr COOK, Auteur ; J. A. SWEENEY, Auteur ; M. W. MOSCONI, Auteur . - 47 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 47 p. Index. décimale : PER Périodiques Résumé : Background: Diminished cognitive control, including reduced behavioral flexibility and behavioral response inhibition, has been repeatedly documented in autism spectrum disorder (ASD). We evaluated behavioral flexibility and response inhibition in probands and their parents using a family trio design to determine the extent to which these cognitive control impairments represent familial traits associated with ASD. Methods: We examined 66 individuals with ASD (probands), 135 unaffected biological parents, and 76 typically developing controls. Participants completed a probabilistic reversal learning task (PRL) and a stop-signal task (SST) to assess behavioral flexibility and response inhibition respectively. Rates of PRL and SST errors were examined across groups, within families, and in relation to clinical and subclinical traits of ASD. Based on prior findings that subclinical broader autism phenotypic (BAP) traits may co-segregate within families and reflect heritable risk factors, we also examined whether cognitive control deficits were more prominent in families in which parents showed BAP features (BAP+). Results: Probands and parents each showed increased rates of PRL and SST errors relative to controls. Error rates across tasks were not related. SST error rates inter-correlated among probands and their parents. PRL errors were more severe in BAP+ parents and their children relative to BAP- parents and their children. For probands of BAP+ parents, PRL and SST error rates were associated with more severe social-communication abnormalities and repetitive behaviors, respectively. Conclusion: Reduced behavioral flexibility and response inhibition are present among probands and their unaffected parents, but represent unique familial deficits associated with ASD that track with separate clinical issues. Specifically, behavioral response inhibition impairments are familial in ASD and manifest independently from parental subclinical features. In contrast, behavioral flexibility deficits are selectively present in families with BAP characteristics, suggesting they co-segregate in families with parental subclinical social, communication, and rigid personality traits. Together, these findings provide evidence that behavioral flexibility and response inhibition impairments track differentially with ASD risk mechanisms and related behavioral traits. En ligne : http://dx.doi.org/10.1186/s13229-019-0296-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Deviation from normative brain development is associated with symptom severity in autism spectrum disorder / B. TUNC in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 46 p. Titre : Deviation from normative brain development is associated with symptom severity in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : B. TUNC, Auteur ; L. D. YANKOWITZ, Auteur ; D. PARKER, Auteur ; J. A. ALAPPATT, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; R. VERMA, Auteur Article en page(s) : 46 p. Langues : Anglais (eng) Mots-clés : Autism  Brain development  Heterogeneity  Machine learning  Normative modeling  Symptom severity Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. The degree to which the brain development in ASD deviates from typical brain development, and how this deviation relates to observed behavioral outcomes at the individual level are not well-studied. We hypothesize that the degree of deviation from typical brain development of an individual with ASD would relate to observed symptom severity. Methods: The developmental changes in anatomical (cortical thickness, surface area, and volume) and diffusion metrics (fractional anisotropy and apparent diffusion coefficient) were compared between a sample of ASD (n = 247) and typically developing children (TDC) (n = 220) aged 6-25. Machine learning was used to predict age (brain age) from these metrics in the TDC sample, to define a normative model of brain development. This model was then used to compute brain age in the ASD sample. The difference between chronological age and brain age was considered a developmental deviation index (DDI), which was then correlated with ASD symptom severity. Results: Machine learning model trained on all five metrics accurately predicted age in the TDC (r = 0.88) and the ASD (r = 0.85) samples, with dominant contributions to the model from the diffusion metrics. Within the ASD group, the DDI derived from fractional anisotropy was correlated with ASD symptom severity (r = - 0.2), such that individuals with the most advanced brain age showing the lowest severity, and individuals with the most delayed brain age showing the highest severity. Limitations: This work investigated only linear relationships between five specific brain metrics and only one measure of ASD symptom severity in a limited age range. Reported effect sizes are moderate. Further work is needed to investigate developmental differences in other age ranges, other aspects of behavior, other neurobiological measures, and in an independent sample before results can be clinically applicable. Conclusions: Findings demonstrate that the degree of deviation from typical brain development relates to ASD symptom severity, partially accounting for the observed heterogeneity in ASD. Our approach enables characterization of each individual with reference to normative brain development and identification of distinct developmental subtypes, facilitating a better understanding of developmental heterogeneity in ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0301-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Deviation from normative brain development is associated with symptom severity in autism spectrum disorder [Texte imprimé et/ou numérique] / B. TUNC, Auteur ; L. D. YANKOWITZ, Auteur ; D. PARKER, Auteur ; J. A. ALAPPATT, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; R. VERMA, Auteur . - 46 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 46 p. Mots-clés : Autism  Brain development  Heterogeneity  Machine learning  Normative modeling  Symptom severity Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. The degree to which the brain development in ASD deviates from typical brain development, and how this deviation relates to observed behavioral outcomes at the individual level are not well-studied. We hypothesize that the degree of deviation from typical brain development of an individual with ASD would relate to observed symptom severity. Methods: The developmental changes in anatomical (cortical thickness, surface area, and volume) and diffusion metrics (fractional anisotropy and apparent diffusion coefficient) were compared between a sample of ASD (n = 247) and typically developing children (TDC) (n = 220) aged 6-25. Machine learning was used to predict age (brain age) from these metrics in the TDC sample, to define a normative model of brain development. This model was then used to compute brain age in the ASD sample. The difference between chronological age and brain age was considered a developmental deviation index (DDI), which was then correlated with ASD symptom severity. Results: Machine learning model trained on all five metrics accurately predicted age in the TDC (r = 0.88) and the ASD (r = 0.85) samples, with dominant contributions to the model from the diffusion metrics. Within the ASD group, the DDI derived from fractional anisotropy was correlated with ASD symptom severity (r = - 0.2), such that individuals with the most advanced brain age showing the lowest severity, and individuals with the most delayed brain age showing the highest severity. Limitations: This work investigated only linear relationships between five specific brain metrics and only one measure of ASD symptom severity in a limited age range. Reported effect sizes are moderate. Further work is needed to investigate developmental differences in other age ranges, other aspects of behavior, other neurobiological measures, and in an independent sample before results can be clinically applicable. Conclusions: Findings demonstrate that the degree of deviation from typical brain development relates to ASD symptom severity, partially accounting for the observed heterogeneity in ASD. Our approach enables characterization of each individual with reference to normative brain development and identification of distinct developmental subtypes, facilitating a better understanding of developmental heterogeneity in ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0301-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Autism and the right to education in the EU: policy mapping and scoping review of Nordic countries Denmark, Finland, and Sweden / R. VAN KESSEL in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 44 p. Titre : Autism and the right to education in the EU: policy mapping and scoping review of Nordic countries Denmark, Finland, and Sweden Type de document : Texte imprimé et/ou numérique Auteurs : R. VAN KESSEL, Auteur ; S. WALSH, Auteur ; A. N. V. RUIGROK, Auteur ; R. HOLT, Auteur ; A. YLIHERVA, Auteur ; E. KARNA, Auteur ; I. MOILANEN, Auteur ; E. HJORNE, Auteur ; S. T. JOHANSSON, Auteur ; Diana SCHENDEL, Auteur ; L. PEDERSEN, Auteur ; M. JORGENSEN, Auteur ; Carol BRAYNE, Auteur ; Simon BARON-COHEN, Auteur ; A. ROMAN-URRESTARAZU, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Introduction: The universal right to education for people with disabilities has been highlighted by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies addressing the right to education and special education needs of autistic children in Denmark, Sweden, and Finland. Methods: A policy path analysis was carried out using a scoping review as an underlying framework for data gathering. Policy mapping was performed independently by both lead authors to increase reliability. Results and discussion: The values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities have been closely translated into the respective education systems of the countries under study, offering special education needs services and support in mainstream education with the aim of including as many children into mainstream education as possible. Even though the education systems are comparable, the approaches between the countries under study are slightly different. Denmark and Sweden have passed several policies specifically geared towards special education needs, while Finland incorporates this more in general education policy. Conclusion: All countries under study have incorporated the values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities in their respective education systems while emphasising the need to include as many children in the mainstream system as possible. En ligne : http://dx.doi.org/10.1186/s13229-019-0290-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Autism and the right to education in the EU: policy mapping and scoping review of Nordic countries Denmark, Finland, and Sweden [Texte imprimé et/ou numérique] / R. VAN KESSEL, Auteur ; S. WALSH, Auteur ; A. N. V. RUIGROK, Auteur ; R. HOLT, Auteur ; A. YLIHERVA, Auteur ; E. KARNA, Auteur ; I. MOILANEN, Auteur ; E. HJORNE, Auteur ; S. T. JOHANSSON, Auteur ; Diana SCHENDEL, Auteur ; L. PEDERSEN, Auteur ; M. JORGENSEN, Auteur ; Carol BRAYNE, Auteur ; Simon BARON-COHEN, Auteur ; A. ROMAN-URRESTARAZU, Auteur . - 44 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 44 p. Index. décimale : PER Périodiques Résumé : Introduction: The universal right to education for people with disabilities has been highlighted by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies addressing the right to education and special education needs of autistic children in Denmark, Sweden, and Finland. Methods: A policy path analysis was carried out using a scoping review as an underlying framework for data gathering. Policy mapping was performed independently by both lead authors to increase reliability. Results and discussion: The values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities have been closely translated into the respective education systems of the countries under study, offering special education needs services and support in mainstream education with the aim of including as many children into mainstream education as possible. Even though the education systems are comparable, the approaches between the countries under study are slightly different. Denmark and Sweden have passed several policies specifically geared towards special education needs, while Finland incorporates this more in general education policy. Conclusion: All countries under study have incorporated the values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities in their respective education systems while emphasising the need to include as many children in the mainstream system as possible. En ligne : http://dx.doi.org/10.1186/s13229-019-0290-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature / A. KOLEVZON in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 50 p. Titre : Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature Type de document : Texte imprimé et/ou numérique Auteurs : A. KOLEVZON, Auteur ; E. DELABY, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; Catalina BETANCUR, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : 22q13 deletion syndrome  Bipolar disorder  Catatonia  Phelan-McDermid syndrome  Psychosis  Regression  SHANK3 Index. décimale : PER Périodiques Résumé : Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.33 and is characterized by intellectual disability, hypotonia, severe speech impairments, and autism spectrum disorder. Emerging evidence indicates that there are changes over time in the phenotype observed in individuals with PMS, including severe neuropsychiatric symptoms and loss of skills occurring in adolescence and adulthood. To gain further insight into these phenomena and to better understand the long-term course of the disorder, we conducted a systematic literature review and identified 56 PMS cases showing signs of behavioral and neurologic decompensation in adolescence or adulthood (30 females, 25 males, 1 gender unknown). Clinical presentations included features of bipolar disorder, catatonia, psychosis, and loss of skills, occurring at a mean age of 20 years. There were no apparent sex differences in the rates of these disorders except for catatonia, which appeared to be more frequent in females (13 females, 3 males). Reports of individuals with point mutations in SHANK3 exhibiting neuropsychiatric decompensation and loss of skills demonstrate that loss of one copy of SHANK3 is sufficient to cause these manifestations. In the majority of cases, no apparent cause could be identified; in others, symptoms appeared after acute events, such as infections, prolonged or particularly intense seizures, or changes in the individual's environment. Several individuals had a progressive neurological deterioration, including one with juvenile onset metachromatic leukodystrophy, a severe demyelinating disorder caused by recessive mutations in the ARSA gene in 22q13.33. These reports provide insights into treatment options that have proven helpful in some cases, and are reviewed herein. Our survey highlights how little is currently known about neuropsychiatric presentations and loss of skills in PMS and underscores the importance of studying the natural history in individuals with PMS, including both cross-sectional and long-term longitudinal analyses. Clearer delineation of these neuropsychiatric symptoms will contribute to their recognition and prompt management and will also help uncover the underlying biological mechanisms, potentially leading to improved interventions. En ligne : http://dx.doi.org/10.1186/s13229-019-0291-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature [Texte imprimé et/ou numérique] / A. KOLEVZON, Auteur ; E. DELABY, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; Catalina BETANCUR, Auteur . - 50 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 50 p. Mots-clés : 22q13 deletion syndrome  Bipolar disorder  Catatonia  Phelan-McDermid syndrome  Psychosis  Regression  SHANK3 Index. décimale : PER Périodiques Résumé : Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.33 and is characterized by intellectual disability, hypotonia, severe speech impairments, and autism spectrum disorder. Emerging evidence indicates that there are changes over time in the phenotype observed in individuals with PMS, including severe neuropsychiatric symptoms and loss of skills occurring in adolescence and adulthood. To gain further insight into these phenomena and to better understand the long-term course of the disorder, we conducted a systematic literature review and identified 56 PMS cases showing signs of behavioral and neurologic decompensation in adolescence or adulthood (30 females, 25 males, 1 gender unknown). Clinical presentations included features of bipolar disorder, catatonia, psychosis, and loss of skills, occurring at a mean age of 20 years. There were no apparent sex differences in the rates of these disorders except for catatonia, which appeared to be more frequent in females (13 females, 3 males). Reports of individuals with point mutations in SHANK3 exhibiting neuropsychiatric decompensation and loss of skills demonstrate that loss of one copy of SHANK3 is sufficient to cause these manifestations. In the majority of cases, no apparent cause could be identified; in others, symptoms appeared after acute events, such as infections, prolonged or particularly intense seizures, or changes in the individual's environment. Several individuals had a progressive neurological deterioration, including one with juvenile onset metachromatic leukodystrophy, a severe demyelinating disorder caused by recessive mutations in the ARSA gene in 22q13.33. These reports provide insights into treatment options that have proven helpful in some cases, and are reviewed herein. Our survey highlights how little is currently known about neuropsychiatric presentations and loss of skills in PMS and underscores the importance of studying the natural history in individuals with PMS, including both cross-sectional and long-term longitudinal analyses. Clearer delineation of these neuropsychiatric symptoms will contribute to their recognition and prompt management and will also help uncover the underlying biological mechanisms, potentially leading to improved interventions. En ligne : http://dx.doi.org/10.1186/s13229-019-0291-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Development of the Stanford Social Dimensions Scale: initial validation in autism spectrum disorder and in neurotypicals / J. M. PHILLIPS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 48 p. Titre : Development of the Stanford Social Dimensions Scale: initial validation in autism spectrum disorder and in neurotypicals Type de document : Texte imprimé et/ou numérique Auteurs : J. M. PHILLIPS, Auteur ; M. ULJAREVIC, Auteur ; R. K. SCHUCK, Auteur ; S. SCHAPP, Auteur ; E. M. SOLOMON, Auteur ; E. SALZMAN, Auteur ; Lauren ALLERHAND, Auteur ; R. A. LIBOVE, Auteur ; T. W. FRAZIER, Auteur ; A. Y. HARDAN, Auteur Article en page(s) : 48 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Social motivation  Social processing Index. décimale : PER Périodiques Résumé : Background: The aim of this paper was to provide an initial validation of a newly developed parent questionnaire-the Stanford Social Dimensions Scale (SSDS), designed to capture individual differences across several key social dimensions including social motivation in children and adolescents with and without psychiatric disorders. Methods: The initial validation sample was comprised of parents of 175 individuals with autism spectrum disorder (ASD) (35 females, 140 males; M age = 7.19 years, SD age = 3.96) and the replication sample consisted of 624 parents of children who were either typically developing or presented with a range of neurodevelopmental and neuropsychiatric disorders (302 females, 322 males; M age = 11.49 years, SDage = 4.48). Parents from both samples completed the SSDS and the Social Responsiveness Scale (SRS-2). Results: Exploratory Structural Equation Modeling indicated that a 5-factor model provided adequate to excellent fit to the data in the initial ASD sample (comparative fit index [CFI] = .940, Tucker-Lewis Index [TLI] = .919, root mean square error of approximation [RMSEA] = .048, standardized root mean square residual [SRMR] = .038). The identified factors were interpreted as Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach. This factor structure was further confirmed in Sample 2 (CFI = 946, TLI = .930, RMSEA = .044, SRMR = .026). Internal consistency for all subscales was in the good to excellent range across both samples as indicated by Composite Reliability scores of >/= .72. Convergent and divergent validity was strong as indexed by the pattern of correlations with relevant SRS-2 and Child Behavior Checklist domains and with verbal and non-verbal intellectual functioning scores in Sample 1 and with the Need to Belong Scale and Child Social Preference Scale scores in Sample 2. Across both samples, females had higher social motivation and expressive social communication scores. Discriminant validity was strong given that across all SSDS subscales, the ASD sample had significantly higher impairment than both the typically developing group and the group with other clinical conditions, which in turn, had significantly higher impairment than the typically developing group. Conclusions: Our findings provide initial validation of a new scale designed to comprehensively capture individual differences in social motivation and other key social dimensions in ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0298-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Development of the Stanford Social Dimensions Scale: initial validation in autism spectrum disorder and in neurotypicals [Texte imprimé et/ou numérique] / J. M. PHILLIPS, Auteur ; M. ULJAREVIC, Auteur ; R. K. SCHUCK, Auteur ; S. SCHAPP, Auteur ; E. M. SOLOMON, Auteur ; E. SALZMAN, Auteur ; Lauren ALLERHAND, Auteur ; R. A. LIBOVE, Auteur ; T. W. FRAZIER, Auteur ; A. Y. HARDAN, Auteur . - 48 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 48 p. Mots-clés : Autism spectrum disorder  Social motivation  Social processing Index. décimale : PER Périodiques Résumé : Background: The aim of this paper was to provide an initial validation of a newly developed parent questionnaire-the Stanford Social Dimensions Scale (SSDS), designed to capture individual differences across several key social dimensions including social motivation in children and adolescents with and without psychiatric disorders. Methods: The initial validation sample was comprised of parents of 175 individuals with autism spectrum disorder (ASD) (35 females, 140 males; M age = 7.19 years, SD age = 3.96) and the replication sample consisted of 624 parents of children who were either typically developing or presented with a range of neurodevelopmental and neuropsychiatric disorders (302 females, 322 males; M age = 11.49 years, SDage = 4.48). Parents from both samples completed the SSDS and the Social Responsiveness Scale (SRS-2). Results: Exploratory Structural Equation Modeling indicated that a 5-factor model provided adequate to excellent fit to the data in the initial ASD sample (comparative fit index [CFI] = .940, Tucker-Lewis Index [TLI] = .919, root mean square error of approximation [RMSEA] = .048, standardized root mean square residual [SRMR] = .038). The identified factors were interpreted as Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach. This factor structure was further confirmed in Sample 2 (CFI = 946, TLI = .930, RMSEA = .044, SRMR = .026). Internal consistency for all subscales was in the good to excellent range across both samples as indicated by Composite Reliability scores of >/= .72. Convergent and divergent validity was strong as indexed by the pattern of correlations with relevant SRS-2 and Child Behavior Checklist domains and with verbal and non-verbal intellectual functioning scores in Sample 1 and with the Need to Belong Scale and Child Social Preference Scale scores in Sample 2. Across both samples, females had higher social motivation and expressive social communication scores. Discriminant validity was strong given that across all SSDS subscales, the ASD sample had significantly higher impairment than both the typically developing group and the group with other clinical conditions, which in turn, had significantly higher impairment than the typically developing group. Conclusions: Our findings provide initial validation of a new scale designed to comprehensively capture individual differences in social motivation and other key social dimensions in ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0298-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Biological motion perception in autism spectrum disorder: a meta-analysis / G. K. TODOROVA in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 49 p. Titre : Biological motion perception in autism spectrum disorder: a meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : G. K. TODOROVA, Auteur ; R. E. M. HATTON, Auteur ; F. E. POLLICK, Auteur Article en page(s) : 49 p. Langues : Anglais (eng) Mots-clés : Age  Autism spectrum disorders  Biological motion  Emotion recognition  Meta-analysis Index. décimale : PER Périodiques Résumé : Background: Biological motion, namely the movement of others, conveys information that allows the identification of affective states and intentions. This makes it an important avenue of research in autism spectrum disorder where social functioning is one of the main areas of difficulty. We aimed to create a quantitative summary of previous findings and investigate potential factors, which could explain the variable results found in the literature investigating biological motion perception in autism. Methods: A search from five electronic databases yielded 52 papers eligible for a quantitative summarisation, including behavioural, eye-tracking, electroencephalography and functional magnetic resonance imaging studies. Results: Using a three-level random effects meta-analytic approach, we found that individuals with autism generally showed decreased performance in perception and interpretation of biological motion. Results additionally suggest decreased performance when higher order information, such as emotion, is required. Moreover, with the increase of age, the difference between autistic and neurotypical individuals decreases, with children showing the largest effect size overall. Conclusion: We highlight the need for methodological standards and clear distinctions between the age groups and paradigms utilised when trying to interpret differences between the two populations. En ligne : http://dx.doi.org/10.1186/s13229-019-0299-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Biological motion perception in autism spectrum disorder: a meta-analysis [Texte imprimé et/ou numérique] / G. K. TODOROVA, Auteur ; R. E. M. HATTON, Auteur ; F. E. POLLICK, Auteur . - 49 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 49 p. Mots-clés : Age  Autism spectrum disorders  Biological motion  Emotion recognition  Meta-analysis Index. décimale : PER Périodiques Résumé : Background: Biological motion, namely the movement of others, conveys information that allows the identification of affective states and intentions. This makes it an important avenue of research in autism spectrum disorder where social functioning is one of the main areas of difficulty. We aimed to create a quantitative summary of previous findings and investigate potential factors, which could explain the variable results found in the literature investigating biological motion perception in autism. Methods: A search from five electronic databases yielded 52 papers eligible for a quantitative summarisation, including behavioural, eye-tracking, electroencephalography and functional magnetic resonance imaging studies. Results: Using a three-level random effects meta-analytic approach, we found that individuals with autism generally showed decreased performance in perception and interpretation of biological motion. Results additionally suggest decreased performance when higher order information, such as emotion, is required. Moreover, with the increase of age, the difference between autistic and neurotypical individuals decreases, with children showing the largest effect size overall. Conclusion: We highlight the need for methodological standards and clear distinctions between the age groups and paradigms utilised when trying to interpret differences between the two populations. En ligne : http://dx.doi.org/10.1186/s13229-019-0299-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells / S. AVAZZADEH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 52 p. Titre : Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells Type de document : Texte imprimé et/ou numérique Auteurs : S. AVAZZADEH, Auteur ; K. MCDONAGH, Auteur ; J. REILLY, Auteur ; Y. WANG, Auteur ; S. D. BOOMKAMP, Auteur ; V. MCINERNEY, Auteur ; J. KRAWCZYK, Auteur ; J. FITZGERALD, Auteur ; N. FEERICK, Auteur ; M. O'SULLIVAN, Auteur ; A. JALALI, Auteur ; E. B. FORMAN, Auteur ; S. A. LYNCH, Auteur ; S. ENNIS, Auteur ; N. COSEMANS, Auteur ; H. PEETERS, Auteur ; P. DOCKERY, Auteur ; T. O'BRIEN, Auteur ; L. R. QUINLAN, Auteur ; L. GALLAGHER, Auteur ; S. SHEN, Auteur Article en page(s) : 52 p. Langues : Anglais (eng) Mots-clés : Autism  Calcium signaling  Induced pluripotent stem cells  NRXN1alpha  Neurons  Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells [Texte imprimé et/ou numérique] / S. AVAZZADEH, Auteur ; K. MCDONAGH, Auteur ; J. REILLY, Auteur ; Y. WANG, Auteur ; S. D. BOOMKAMP, Auteur ; V. MCINERNEY, Auteur ; J. KRAWCZYK, Auteur ; J. FITZGERALD, Auteur ; N. FEERICK, Auteur ; M. O'SULLIVAN, Auteur ; A. JALALI, Auteur ; E. B. FORMAN, Auteur ; S. A. LYNCH, Auteur ; S. ENNIS, Auteur ; N. COSEMANS, Auteur ; H. PEETERS, Auteur ; P. DOCKERY, Auteur ; T. O'BRIEN, Auteur ; L. R. QUINLAN, Auteur ; L. GALLAGHER, Auteur ; S. SHEN, Auteur . - 52 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 52 p. Mots-clés : Autism  Calcium signaling  Induced pluripotent stem cells  NRXN1alpha  Neurons  Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons / E. M. A. LEWIS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 51 p. Titre : Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons Type de document : Texte imprimé et/ou numérique Auteurs : E. M. A. LEWIS, Auteur ; K. MEGANATHAN, Auteur ; D. BALDRIDGE, Auteur ; P. GONTARZ, Auteur ; B. ZHANG, Auteur ; A. BONNI, Auteur ; John N. CONSTANTINO, Auteur ; K. L. KROLL, Auteur Article en page(s) : 51 p. Langues : Anglais (eng) Mots-clés : Cortical excitatory neurons  Cortical inhibitory neurons  Gene networks  Multiplex autism  Neurodevelopment  Transcriptomics  iPSC modeling Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with pronounced heritability in the general population. This is largely attributable to the effects of polygenic susceptibility, with inherited liability exhibiting distinct sex differences in phenotypic expression. Attempts to model ASD in human cellular systems have principally involved rare de novo mutations associated with ASD phenocopies. However, by definition, these models are not representative of polygenic liability, which accounts for the vast share of population-attributable risk. Methods: Here, we performed what is, to our knowledge, the first attempt to model multiplex autism using patient-derived induced pluripotent stem cells (iPSCs) in a family manifesting incremental degrees of phenotypic expression of inherited liability (absent, intermediate, severe). The family members share an inherited variant of uncertain significance (VUS) in GPD2, a gene that was previously associated with developmental disability but here is insufficient by itself to cause ASD. iPSCs from three first-degree relatives and an unrelated control were differentiated into both cortical excitatory (cExN) and cortical inhibitory (cIN) neurons, and cellular phenotyping and transcriptomic analysis were conducted. Results: cExN neurospheres from the two affected individuals were reduced in size, compared to those derived from unaffected related and unrelated individuals. This reduction was, at least in part, due to increased apoptosis of cells from affected individuals upon initiation of cExN neural induction. Likewise, cIN neural progenitor cells from affected individuals exhibited increased apoptosis, compared to both unaffected individuals. Transcriptomic analysis of both cExN and cIN neural progenitor cells revealed distinct molecular signatures associated with affectation, including the misregulation of suites of genes associated with neural development, neuronal function, and behavior, as well as altered expression of ASD risk-associated genes. Conclusions: We have provided evidence of morphological, physiological, and transcriptomic signatures of polygenic liability to ASD from an analysis of cellular models derived from a multiplex autism family. ASD is commonly inherited on the basis of additive genetic liability. Therefore, identifying convergent cellular and molecular phenotypes resulting from polygenic and monogenic susceptibility may provide a critical bridge for determining which of the disparate effects of rare highly deleterious mutations might also apply to common autistic syndromes. En ligne : http://dx.doi.org/10.1186/s13229-019-0306-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons [Texte imprimé et/ou numérique] / E. M. A. LEWIS, Auteur ; K. MEGANATHAN, Auteur ; D. BALDRIDGE, Auteur ; P. GONTARZ, Auteur ; B. ZHANG, Auteur ; A. BONNI, Auteur ; John N. CONSTANTINO, Auteur ; K. L. KROLL, Auteur . - 51 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 51 p. Mots-clés : Cortical excitatory neurons  Cortical inhibitory neurons  Gene networks  Multiplex autism  Neurodevelopment  Transcriptomics  iPSC modeling Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with pronounced heritability in the general population. This is largely attributable to the effects of polygenic susceptibility, with inherited liability exhibiting distinct sex differences in phenotypic expression. Attempts to model ASD in human cellular systems have principally involved rare de novo mutations associated with ASD phenocopies. However, by definition, these models are not representative of polygenic liability, which accounts for the vast share of population-attributable risk. Methods: Here, we performed what is, to our knowledge, the first attempt to model multiplex autism using patient-derived induced pluripotent stem cells (iPSCs) in a family manifesting incremental degrees of phenotypic expression of inherited liability (absent, intermediate, severe). The family members share an inherited variant of uncertain significance (VUS) in GPD2, a gene that was previously associated with developmental disability but here is insufficient by itself to cause ASD. iPSCs from three first-degree relatives and an unrelated control were differentiated into both cortical excitatory (cExN) and cortical inhibitory (cIN) neurons, and cellular phenotyping and transcriptomic analysis were conducted. Results: cExN neurospheres from the two affected individuals were reduced in size, compared to those derived from unaffected related and unrelated individuals. This reduction was, at least in part, due to increased apoptosis of cells from affected individuals upon initiation of cExN neural induction. Likewise, cIN neural progenitor cells from affected individuals exhibited increased apoptosis, compared to both unaffected individuals. Transcriptomic analysis of both cExN and cIN neural progenitor cells revealed distinct molecular signatures associated with affectation, including the misregulation of suites of genes associated with neural development, neuronal function, and behavior, as well as altered expression of ASD risk-associated genes. Conclusions: We have provided evidence of morphological, physiological, and transcriptomic signatures of polygenic liability to ASD from an analysis of cellular models derived from a multiplex autism family. ASD is commonly inherited on the basis of additive genetic liability. Therefore, identifying convergent cellular and molecular phenotypes resulting from polygenic and monogenic susceptibility may provide a critical bridge for determining which of the disparate effects of rare highly deleterious mutations might also apply to common autistic syndromes. En ligne : http://dx.doi.org/10.1186/s13229-019-0306-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414